7-150743155-G-C

Variant names:

• chr7-150743155-G-C
• rs10361
• ENST00000476324.1:n.4291G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000476324.1(GIMAP5):​n.4291G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,469,250 control chromosomes in the GnomAD database, including 73,330 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11390 hom., cov: 31)
  • Exomes 𝑓: 0.30 (61940 hom.)
• Consequence: GIMAP5 ENST00000476324.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 14 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.*92G>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.*92G>C		3_prime_UTR_variant	Exon 6 of 6		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.*92G>C		3_prime_UTR_variant	Exon 5 of 5		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.*92G>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.*92G>C		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56240 AN: 151782 Hom.: 11372 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.304 AC: 400519 AN: 1317350 Hom.: 61940 Cov.: 21 AF XY: 0.303 AC XY: 196260 AN XY: 648170

African (AFR) AF: 0.545 AC: 16243 AN: 29796

American (AMR) AF: 0.236 AC: 7706 AN: 32696

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 6654 AN: 20364

East Asian (EAS) AF: 0.275 AC: 10654 AN: 38714

South Asian (SAS) AF: 0.259 AC: 17709 AN: 68344

European-Finnish (FIN) AF: 0.390 AC: 14712 AN: 37690

Middle Eastern (MID) AF: 0.334 AC: 1677 AN: 5028

European-Non Finnish (NFE) AF: 0.300 AC: 308517 AN: 1029874

Other (OTH) AF: 0.304 AC: 16647 AN: 54844

GnomAD4 genome AF: 0.371 AC: 56313 AN: 151900 Hom.: 11390 Cov.: 31 AF XY: 0.372 AC XY: 27583 AN XY: 74218

African (AFR) AF: 0.536 AC: 22183 AN: 41386

American (AMR) AF: 0.280 AC: 4282 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1196 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1470 AN: 5176

South Asian (SAS) AF: 0.266 AC: 1279 AN: 4808

European-Finnish (FIN) AF: 0.401 AC: 4228 AN: 10546

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20698 AN: 67934

Other (OTH) AF: 0.342 AC: 721 AN: 2108

Alfa AF: 0.197 Hom.: 434

Bravo AF: 0.370

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.57
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10361; hg19: chr7-150440243; COSMIC: COSV57529642; COSMIC: COSV57529642;