rs4725359

Positions:

• chr7-150741050-G-A

Variant summary

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

The NM_018384.5(GIMAP5):​c.43+123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 962,822 control chromosomes in the GnomAD database, including 7,804 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 0.14 (1490 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6314 hom.)
• Consequence: GIMAP5 NM_018384.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.43+123G>A		intron_variant		ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.655+123G>A		intron_variant			NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.271+123G>A		intron_variant			NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.43+123G>A		intron_variant		1	NM_018384.5	ENSP00000351473	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20512 AN: 151938 Hom.: 1483 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0907

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.122 AC: 98577 AN: 810766 Hom.: 6314 AF XY: 0.120 AC XY: 50380 AN XY: 419720

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.0529

Gnomad4 EAS exome AF: 0.0872

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.135 AC: 20549 AN: 152056 Hom.: 1490 Cov.: 32 AF XY: 0.137 AC XY: 10182 AN XY: 74324

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.0911

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.128

Alfa AF: 0.124 Hom.: 175

Bravo AF: 0.137

Asia WGS AF: 0.104 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.68

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: rs4725359; hg19: chr7-150438138; COSMIC: COSV62280785; COSMIC: COSV62280785;