rs6598

Positions:

• chr7-150743561-G-A
• chr7-150743561-G-C
• chr7-150743561-G-T

Variant summary

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

The NM_018384.5(GIMAP5):​c.*498G>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 0.38 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 NM_018384.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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]

GIMAP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.*498G>A		3_prime_UTR_variant	3/3	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.*498G>A		3_prime_UTR_variant	6/6		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.*498G>A		3_prime_UTR_variant	5/5		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.*498G>A		3_prime_UTR_variant	3/3	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.*498G>A		3_prime_UTR_variant	6/6	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

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.0714

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.226

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

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.350

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

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: rs6598; hg19: chr7-150440649;