rs9657886

Variant names:

• chr7-150741470-G-T
• rs9657886
• NM_018384.5:c.43+543G>T

Variant summary

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

The NM_018384.5(GIMAP5):​c.43+543G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,004 control chromosomes in the GnomAD database, including 7,661 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 0.31 (7661 hom., cov: 32)
• Consequence: GIMAP5 NM_018384.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.43+543G>T		intron_variant	Intron 2 of 2	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.655+543G>T		intron_variant	Intron 5 of 5		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.271+543G>T		intron_variant	Intron 4 of 4		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.43+543G>T		intron_variant	Intron 2 of 2	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.655+543G>T		intron_variant	Intron 5 of 5	5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47579 AN: 151886 Hom.: 7655 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.313 AC: 47627 AN: 152004 Hom.: 7661 Cov.: 32 AF XY: 0.316 AC XY: 23496 AN XY: 74280

African (AFR) AF: 0.337 AC: 13978 AN: 41444

American (AMR) AF: 0.260 AC: 3978 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1411 AN: 5172

South Asian (SAS) AF: 0.243 AC: 1169 AN: 4812

European-Finnish (FIN) AF: 0.401 AC: 4230 AN: 10558

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20827 AN: 67956

Other (OTH) AF: 0.303 AC: 638 AN: 2108

Alfa AF: 0.304 Hom.: 10291

Bravo AF: 0.303

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.57
PhyloP100		-1.3
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: rs9657886; hg19: chr7-150438558; COSMIC: COSV107439514; COSMIC: COSV107439514;