rs4725359

Variant names:

• chr7-150741050-G-A
• rs4725359
• NM_018384.5:c.43+123G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.82).
• 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 rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.43+123G>A		intron_variant	Intron 2 of 2	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.655+123G>A		intron_variant	Intron 5 of 5		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.271+123G>A		intron_variant	Intron 4 of 4		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.43+123G>A		intron_variant	Intron 2 of 2	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.655+123G>A		intron_variant	Intron 5 of 5	5		ENSP00000477920.1

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

African (AFR) AF: 0.182 AC: 3554 AN: 19492

American (AMR) AF: 0.193 AC: 5880 AN: 30500

Ashkenazi Jewish (ASJ) AF: 0.0529 AC: 1025 AN: 19382

East Asian (EAS) AF: 0.0872 AC: 2921 AN: 33498

South Asian (SAS) AF: 0.101 AC: 6296 AN: 62110

European-Finnish (FIN) AF: 0.149 AC: 7000 AN: 47038

Middle Eastern (MID) AF: 0.0864 AC: 384 AN: 4442

European-Non Finnish (NFE) AF: 0.120 AC: 66734 AN: 555800

Other (OTH) AF: 0.124 AC: 4783 AN: 38504

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

African (AFR) AF: 0.179 AC: 7411 AN: 41448

American (AMR) AF: 0.143 AC: 2192 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3472

East Asian (EAS) AF: 0.0911 AC: 472 AN: 5180

South Asian (SAS) AF: 0.100 AC: 482 AN: 4818

European-Finnish (FIN) AF: 0.154 AC: 1624 AN: 10548

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7788 AN: 67986

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.126 Hom.: 184

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
PhyloP100		0.039
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: rs4725359; hg19: chr7-150438138; COSMIC: COSV62280785; COSMIC: COSV62280785;