chr7-150743561-G-A

Variant names:

• chr7-150743561-G-A
• rs6598
• ENST00000476324.1:n.4697G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000476324.1(GIMAP5):​n.4697G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 153,836 control chromosomes in the GnomAD database, including 12,134 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 0.38 (12086 hom., cov: 32)
  • Exomes 𝑓: 0.23 (48 hom.)
• Consequence: GIMAP5 ENST00000476324.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.*498G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.*498G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.*498G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.*498G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.*498G>A		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57960 AN: 151958 Hom.: 12065 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.230 AC: 404 AN: 1760 Hom.: 48 Cov.: 0 AF XY: 0.222 AC XY: 195 AN XY: 878

African (AFR) AF: 0.357 AC: 5 AN: 14

American (AMR) AF: 0.138 AC: 37 AN: 268

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 3 AN: 8

East Asian (EAS) AF: 0.0714 AC: 1 AN: 14

South Asian (SAS) AF: 0.256 AC: 20 AN: 78

European-Finnish (FIN) AF: 0.400 AC: 12 AN: 30

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.243 AC: 312 AN: 1286

Other (OTH) AF: 0.226 AC: 14 AN: 62

GnomAD4 genome AF: 0.382 AC: 58034 AN: 152076 Hom.: 12086 Cov.: 32 AF XY: 0.384 AC XY: 28566 AN XY: 74306

African (AFR) AF: 0.553 AC: 22933 AN: 41454

American (AMR) AF: 0.285 AC: 4361 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1195 AN: 3466

East Asian (EAS) AF: 0.285 AC: 1470 AN: 5166

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4818

European-Finnish (FIN) AF: 0.401 AC: 4234 AN: 10568

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20940 AN: 67988

Other (OTH) AF: 0.350 AC: 739 AN: 2114

Alfa AF: 0.273 Hom.: 1418

Bravo AF: 0.377

Asia WGS AF: 0.356 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-2.0
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: rs6598; hg19: chr7-150440649;