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:):

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	P1

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;