rs193233179

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001199577.2(GIMAP1-GIMAP5):c.500G>A(p.Arg167His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,535,618 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0054 ( 28 hom. )

Consequence

GIMAP1-GIMAP5
NM_001199577.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

Publications

2 publications found

Variant links:

Genes affected

GIMAP1-GIMAP5 (HGNC:51257): (GIMAP1-GIMAP5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GIMAP1 (GTPase, IMAP family member 1) and GIMAP5 (GTPase, IMAP family member 5) genes on chromosome 7. Alternative splicing results in multiple readthrough transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2015]

GIMAP1-GIMAP5 links:

GIMAP5 (HGNC:18005): (GTPase, IMAP family member 5) This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. In humans, the IAN subfamily genes are located in a cluster at 7q36.1. This gene encodes an antiapoptotic protein that functions in T-cell survival. Polymorphisms in this gene are associated with systemic lupus erythematosus. Read-through transcription exists between this gene and the neighboring upstream GIMAP1 (GTPase, IMAP family member 1) gene. [provided by RefSeq, Dec 2010]

GIMAP5 Gene-Disease associations (from GenCC):

portal hypertension, noncirrhotic, 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

GIMAP5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040815473).

BP6

Variant 7-150737602-G-A is Benign according to our data. Variant chr7-150737602-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3387861.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 28 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199577.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GIMAP5	NM_018384.5	MANE Select	c.-113G>A		5_prime_UTR	Exon 1 of 3	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2		c.500G>A	p.Arg167His	missense	Exon 4 of 6	NP_001186506.1	A0A087WTJ2
GIMAP1-GIMAP5	NM_001303630.2		c.116G>A	p.Arg39His	missense	Exon 3 of 5	NP_001290559.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GIMAP1-GIMAP5	ENST00000611999.4	TSL:5	c.500G>A	p.Arg167His	missense	Exon 4 of 6	ENSP00000477920.1	A0A087WTJ2
GIMAP5	ENST00000358647.5	TSL:1 MANE Select	c.-113G>A		5_prime_UTR	Exon 1 of 3	ENSP00000351473.3	Q96F15-1
GIMAP5	ENST00000498181.6	TSL:4	c.-113G>A		5_prime_UTR	Exon 2 of 4	ENSP00000487840.2	Q96F15-1

Frequencies

GnomAD3 genomes

AF:

0.00324

AC:

493

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00548

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00283

AC:

367

AN:

129566

AF XY:

0.00295

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00223

Gnomad NFE exome

AF:

0.00590

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00540

AC:

7476

AN:

1383354

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

3526

AN XY:

682576

show subpopulations

African (AFR)

AF:

0.000981

AC:

AN:

31594

American (AMR)

AF:

0.00165

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.000397

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.000896

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00200

AC:

AN:

33474

Middle Eastern (MID)

AF:

0.000702

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00649

AC:

7001

AN:

1078840

Other (OTH)

AF:

0.00402

AC:

233

AN:

57900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

440

880

1320

1760

2200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.00324

AC:

493

AN:

152264

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

226

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41560

American (AMR)

AF:

0.00216

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00548

AC:

373

AN:

68012

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00337

Hom.:

Bravo

AF:

0.00328

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00571

AC:

ExAC

AF:

0.00111

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.2

(source)

DANN

Benign

0.81

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0041

PhyloP100

-1.6

PrimateAI

Benign

0.33

Sift4G

Benign

0.15

Vest4

0.058

MVP

0.061

GERP RS

-3.0

PromoterAI

-0.060

Neutral

(source)

gMVP

0.68

Mutation Taster

=300/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over