rs4725936

Positions:

• chr7-150741001-T-C
• chr7-150741001-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018384.5(GIMAP5):​c.43+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,519,160 control chromosomes in the GnomAD database, including 156,318 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 0.53 (23528 hom., cov: 31)
  • Exomes 𝑓: 0.44 (132790 hom.)
• Consequence: GIMAP5 NM_018384.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.43+74T>C		intron_variant		ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.655+74T>C		intron_variant			NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.271+74T>C		intron_variant			NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.43+74T>C		intron_variant		1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.655+74T>C		intron_variant		5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80803 AN: 151798 Hom.: 23485 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.435 AC: 595336 AN: 1367244 Hom.: 132790 AF XY: 0.436 AC XY: 298304 AN XY: 684400

Gnomad4 AFR exome AF: 0.798

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.533 AC: 80918 AN: 151916 Hom.: 23528 Cov.: 31 AF XY: 0.537 AC XY: 39833 AN XY: 74216

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.489

Alfa AF: 0.493 Hom.: 3163

Bravo AF: 0.532

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs4725936; hg19: chr7-150438089; COSMIC: COSV62281487; COSMIC: COSV62281487;