rs6965571

Variant names:

• chr7-150737384-G-A
• rs6965571
• ENST00000611999.4:c.403-121G>A

Variant summary

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

The NM_001199577.2(GIMAP1-GIMAP5):​c.403-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 715,118 control chromosomes in the GnomAD database, including 9,532 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 0.17 (2453 hom., cov: 31)
  • Exomes 𝑓: 0.15 (7079 hom.)
• Consequence: GIMAP1-GIMAP5 NM_001199577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP1-GIMAP5	NM_001199577.2	c.403-121G>A		intron_variant	Intron 3 of 5		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.19-121G>A		intron_variant	Intron 2 of 4		NP_001290559.1
GIMAP5	NM_018384.5	c.-331G>A		upstream_gene_variant		ENST00000358647.5	NP_060854.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP1-GIMAP5	ENST00000611999.4	c.403-121G>A		intron_variant	Intron 3 of 5	5		ENSP00000477920.1
GIMAP5	ENST00000358647.5	c.-331G>A		upstream_gene_variant		1	NM_018384.5	ENSP00000351473.3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26277 AN: 151388 Hom.: 2451 Cov.: 31

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.151 AC: 85387 AN: 563670 Hom.: 7079 Cov.: 7 AF XY: 0.151 AC XY: 44520 AN XY: 295424

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.00631

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.174 AC: 26292 AN: 151448 Hom.: 2453 Cov.: 31 AF XY: 0.170 AC XY: 12532 AN XY: 73894

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0117

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.176

Alfa AF: 0.174 Hom.: 4711

Bravo AF: 0.175

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.59

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: rs6965571; hg19: chr7-150434472;