rs2286900

Positions:

• chr7-150720957-G-A

Variant summary

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

The NM_130759.4(GIMAP1):​c.*32G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 1,475,006 control chromosomes in the GnomAD database, including 7,735 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 0.11 (1010 hom., cov: 32)
  • Exomes 𝑓: 0.099 (6725 hom.)
• Consequence: GIMAP1 NM_130759.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

GIMAP1 (HGNC:23237): (GTPase, IMAP family member 1) 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 is thought to be involved in the differentiation of T helper (Th) cells of the Th1 lineage, and the related mouse gene has been shown to be critical for the development of mature B and T lymphocytes. Read-through transcription exists between this gene and the downstream GIMAP5 (GTPase, IMAP family member 5) 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMAP1	NM_130759.4	c.*32G>A		3_prime_UTR_variant	3/3	ENST00000307194.6	NP_570115.1
GIMAP1-GIMAP5	NM_001199577.2	c.402+551G>A		intron_variant			NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.18+1867G>A		intron_variant			NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP1	ENST00000307194.6	c.*32G>A		3_prime_UTR_variant	3/3	1	NM_130759.4	ENSP00000302833.5
GIMAP1-GIMAP5	ENST00000611999.4	c.402+551G>A		intron_variant		5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16524 AN: 152094 Hom.: 1010 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0974

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.109 AC: 14504 AN: 133184 Hom.: 794 AF XY: 0.106 AC XY: 7787 AN XY: 73538

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0771

Gnomad EAS exome AF: 0.197

Gnomad SAS exome AF: 0.100

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.0960

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.0988 AC: 130675 AN: 1322794 Hom.: 6725 Cov.: 28 AF XY: 0.0987 AC XY: 63901 AN XY: 647636

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0831

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.0986

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0949

Gnomad4 OTH exome AF: 0.0992

GnomAD4 genome AF: 0.109 AC: 16552 AN: 152212 Hom.: 1010 Cov.: 32 AF XY: 0.109 AC XY: 8149 AN XY: 74438

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0972

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0955

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0945 Hom.: 749

Bravo AF: 0.109

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.65

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: rs2286900; hg19: chr7-150418045;