7-150728263-G-T

Position:

• chr7-150728263-G-T

Variant summary

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

The NM_001199577.2(GIMAP1-GIMAP5):​c.402+7857G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,246 control chromosomes in the GnomAD database, including 994 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 (994 hom., cov: 32)
• Consequence: GIMAP1-GIMAP5 NM_001199577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMAP1-GIMAP5	NM_001199577.2	c.402+7857G>T		intron_variant			NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.18+9173G>T		intron_variant			NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP1-GIMAP5	ENST00000611999.4	c.402+7857G>T		intron_variant		5		ENSP00000477920.1
GIMAP5	ENST00000498181.6	c.-211+5893G>T		intron_variant		4		ENSP00000487840.2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16431 AN: 152128 Hom.: 994 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16460 AN: 152246 Hom.: 994 Cov.: 32 AF XY: 0.109 AC XY: 8112 AN XY: 74440

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0945

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0953 Hom.: 769

Bravo AF: 0.109

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.79

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: rs6945478; hg19: chr7-150425351;