7-150742412-C-T

Variant names:

• chr7-150742412-C-T
• rs759011
• NM_018384.5:c.273C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018384.5(GIMAP5):​c.273C>T​(p.Ala91Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,836 control chromosomes in the GnomAD database, including 86,078 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 0.38 (12088 hom., cov: 31)
  • Exomes 𝑓: 0.31 (73990 hom.)
• Consequence: GIMAP5 NM_018384.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44
• Publications: 30 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-3.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.273C>T	p.Ala91Ala	synonymous_variant	Exon 3 of 3	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.885C>T	p.Ala295Ala	synonymous_variant	Exon 6 of 6		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.501C>T	p.Ala167Ala	synonymous_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.273C>T	p.Ala91Ala	synonymous_variant	Exon 3 of 3	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.885C>T	p.Ala295Ala	synonymous_variant	Exon 6 of 6	5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57934 AN: 151852 Hom.: 12067 Cov.: 31

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.348

GnomAD2 exomes AF: 0.328 AC: 82363 AN: 251238 AF XY: 0.330

Gnomad AFR exome AF: 0.557

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.322

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.397

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.314 AC: 458786 AN: 1461866 Hom.: 73990 Cov.: 60 AF XY: 0.316 AC XY: 229759 AN XY: 727232

African (AFR) AF: 0.560 AC: 18749 AN: 33480

American (AMR) AF: 0.236 AC: 10566 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 8493 AN: 26134

East Asian (EAS) AF: 0.276 AC: 10944 AN: 39700

South Asian (SAS) AF: 0.377 AC: 32476 AN: 86256

European-Finnish (FIN) AF: 0.392 AC: 20942 AN: 53416

Middle Eastern (MID) AF: 0.334 AC: 1928 AN: 5768

European-Non Finnish (NFE) AF: 0.302 AC: 335728 AN: 1111992

Other (OTH) AF: 0.314 AC: 18960 AN: 60396

GnomAD4 genome AF: 0.382 AC: 58008 AN: 151970 Hom.: 12088 Cov.: 31 AF XY: 0.385 AC XY: 28559 AN XY: 74252

African (AFR) AF: 0.553 AC: 22927 AN: 41428

American (AMR) AF: 0.285 AC: 4359 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1196 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1461 AN: 5144

South Asian (SAS) AF: 0.395 AC: 1906 AN: 4820

European-Finnish (FIN) AF: 0.401 AC: 4234 AN: 10546

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20930 AN: 67956

Other (OTH) AF: 0.349 AC: 736 AN: 2108

Alfa AF: 0.332 Hom.: 26094

Bravo AF: 0.377

Asia WGS AF: 0.356 AC: 1239 AN: 3478

EpiCase AF: 0.307

EpiControl AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.9
DANN	Benign	0.54
PhyloP100		-3.4
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: rs759011; hg19: chr7-150439500; COSMIC: COSV57529710; COSMIC: COSV57529710;