chr7-150739999-C-T

Variant names:

• chr7-150739999-C-T
• rs11973400
• NM_018384.5:c.-6-880C>T

Variant summary

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

The NM_018384.5(GIMAP5):​c.-6-880C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,038 control chromosomes in the GnomAD database, including 2,684 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 0.18 (2684 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: GIMAP5 NM_018384.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.-6-880C>T		intron_variant	Intron 1 of 2	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.607-880C>T		intron_variant	Intron 4 of 5		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.223-880C>T		intron_variant	Intron 3 of 4		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.-6-880C>T		intron_variant	Intron 1 of 2	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.607-880C>T		intron_variant	Intron 4 of 5	5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27183 AN: 151918 Hom.: 2683 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.179 AC: 27199 AN: 152036 Hom.: 2684 Cov.: 32 AF XY: 0.175 AC XY: 12978 AN XY: 74310

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.176

Alfa AF: 0.172 Hom.: 2411

Bravo AF: 0.182

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
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: rs11973400; hg19: chr7-150437087;