Genetic Variant GORAB-AS1:n.200+422A>G (chr1-170532026-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000456083.5(GORAB-AS1):n.200+422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,277,734 control chromosomes in the GnomAD database, including 33,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3862 hom., cov: 32)

Exomes 𝑓: 0.21 ( 29647 hom. )

Consequence

GORAB-AS1
ENST00000456083.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.56

Variant links:

Genes affected

GORAB-AS1 (HGNC:54051): (GORAB antisense RNA 1)

GORAB-AS1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-170532026-T-C is Benign according to our data. Variant chr1-170532026-T-C is described in ClinVar as [Benign]. Clinvar id is 1241712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GORAB	NM_152281.3 link	c.-198T>C		upstream_gene_variant		ENST00000367763.8	NP_689494.3	Q5T7V8-1B3KQ87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GORAB	ENST00000367763.8 link	c.-198T>C		upstream_gene_variant		2	NM_152281.3	ENSP00000356737.4		Q5T7V8-1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30760

AN:

151954

Hom.:

3854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.0683

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.606

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.211

AC:

237713

AN:

1125662

Hom.:

29647

Cov.:

AF XY:

0.208

AC XY:

119305

AN XY:

572788

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.408

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.588

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.206

GnomAD4 genome

AF:

0.203

AC:

30801

AN:

152072

Hom.:

3862

Cov.:

AF XY:

0.211

AC XY:

15704

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.606

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.194

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.194

Hom.:

6174

Bravo

AF:

0.206

Asia WGS

AF:

0.380

AC:

1321

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 12, 2021

GeneDx

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_noAF

Benign

-0.79

CADD

Benign

0.010

DANN

Benign

0.77

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over