chr1-170552235-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152281.3(GORAB):c.883G>A(p.Glu295Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 1,613,706 control chromosomes in the GnomAD database, including 201,261 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20782 hom., cov: 32)

Exomes 𝑓: 0.49 ( 180479 hom. )

Consequence

GORAB
NM_152281.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.85

Publications

50 publications found

Variant links:

Genes affected

GORAB (HGNC:25676): (golgin, RAB6 interacting) This gene encodes a member of the golgin family, a group of coiled-coil proteins localized to the Golgi. The encoded protein may function in the secretory pathway. The encoded protein, which also localizes to the cytoplasm, was identified by interactions with the N-terminal kinase-like protein, and thus it may function in mitosis. Mutations in this gene have been associated with geroderma osteodysplastica. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

GORAB Gene-Disease associations (from GenCC):

geroderma osteodysplastica
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

GORAB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1499877E-6).

BP6

Variant 1-170552235-G-A is Benign according to our data. Variant chr1-170552235-G-A is described in ClinVar as Benign. ClinVar VariationId is 262629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GORAB	NM_152281.3 link	c.883G>A	p.Glu295Lys	missense_variant	Exon 5 of 5	ENST00000367763.8	NP_689494.3	Q5T7V8-1B3KQ87
GORAB	NM_001410894.1 link	c.832G>A	p.Glu278Lys	missense_variant	Exon 5 of 5		NP_001397823.1
GORAB	NM_001320252.2 link	c.418G>A	p.Glu140Lys	missense_variant	Exon 7 of 7		NP_001307181.1	Q5T7V8B3KQ87
GORAB	NR_027397.2 link	n.945G>A		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GORAB	ENST00000367763.8 link	c.883G>A	p.Glu295Lys	missense_variant	Exon 5 of 5	2	NM_152281.3	ENSP00000356737.4		Q5T7V8-1

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78141

AN:

151876

Hom.:

20750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.521

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.486

GnomAD2 exomes

AF:

0.544

AC:

136688

AN:

251324

AF XY:

0.532

show subpopulations

Gnomad AFR exome

AF:

0.523

Gnomad AMR exome

AF:

0.668

Gnomad ASJ exome

AF:

0.416

Gnomad EAS exome

AF:

0.909

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.473

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.489

AC:

715334

AN:

1461712

Hom.:

180479

Cov.:

AF XY:

0.489

AC XY:

355413

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.515

AC:

17223

AN:

33472

American (AMR)

AF:

0.656

AC:

29319

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

10951

AN:

26136

East Asian (EAS)

AF:

0.921

AC:

36567

AN:

39694

South Asian (SAS)

AF:

0.495

AC:

42711

AN:

86248

European-Finnish (FIN)

AF:

0.560

AC:

29905

AN:

53416

Middle Eastern (MID)

AF:

0.419

AC:

2417

AN:

5768

European-Non Finnish (NFE)

AF:

0.464

AC:

516194

AN:

1111876

Other (OTH)

AF:

0.498

AC:

30047

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

21054

42107

63161

84214

105268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15496

30992

46488

61984

77480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.515

AC:

78226

AN:

151994

Hom.:

20782

Cov.:

AF XY:

0.523

AC XY:

38829

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.524

AC:

21709

AN:

41458

American (AMR)

AF:

0.574

AC:

8762

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1450

AN:

3468

East Asian (EAS)

AF:

0.890

AC:

4606

AN:

5174

South Asian (SAS)

AF:

0.520

AC:

2508

AN:

4820

European-Finnish (FIN)

AF:

0.559

AC:

5900

AN:

10552

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.469

AC:

31868

AN:

67938

Other (OTH)

AF:

0.491

AC:

1037

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1929

3858

5786

7715

9644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.485

Hom.:

71889

Bravo

AF:

0.520

TwinsUK

AF:

0.465

AC:

1726

ALSPAC

AF:

0.470

AC:

1811

ESP6500AA

AF:

0.531

AC:

2340

ESP6500EA

AF:

0.463

AC:

3979

ExAC

AF:

0.539

AC:

65464

Asia WGS

AF:

0.676

AC:

2348

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Geroderma osteodysplastica

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

Eigen

Benign

-0.095

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.82

REVEL

Benign

0.14

Sift

Benign

0.059

Sift4G

Uncertain

0.023

Polyphen

0.78

Vest4

0.073

MPC

0.49

ClinPred

0.027

GERP RS

2.6

Varity_R

0.060

gMVP

0.14

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over