ENST00000476324.1:n.3230C>T

Variant names:

• chr7-150740839-C-T
• rs9657894
• ENST00000476324.1:n.3230C>T

Variant summary

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

The ENST00000476324.1(GIMAP5):​n.3230C>T 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 0.32 in 1,608,372 control chromosomes in the GnomAD database, including 85,861 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 (12080 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73781 hom.)
• Consequence: GIMAP5 ENST00000476324.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.-6-40C>T		intron_variant	Intron 1 of 2	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.607-40C>T		intron_variant	Intron 4 of 5		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.223-40C>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.-6-40C>T		intron_variant	Intron 1 of 2	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.607-40C>T		intron_variant	Intron 4 of 5	5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57936 AN: 151858 Hom.: 12059 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.348

GnomAD2 exomes AF: 0.327 AC: 82076 AN: 250770 AF XY: 0.329

Gnomad AFR exome AF: 0.557

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.267

Gnomad FIN exome AF: 0.397

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.314 AC: 457015 AN: 1456396 Hom.: 73781 Cov.: 29 AF XY: 0.316 AC XY: 228980 AN XY: 724890

African (AFR) AF: 0.560 AC: 18693 AN: 33368

American (AMR) AF: 0.236 AC: 10544 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 8475 AN: 26078

East Asian (EAS) AF: 0.276 AC: 10944 AN: 39662

South Asian (SAS) AF: 0.376 AC: 32371 AN: 86064

European-Finnish (FIN) AF: 0.392 AC: 20919 AN: 53356

Middle Eastern (MID) AF: 0.334 AC: 1921 AN: 5752

European-Non Finnish (NFE) AF: 0.302 AC: 334249 AN: 1107276

Other (OTH) AF: 0.314 AC: 18899 AN: 60176

GnomAD4 genome AF: 0.382 AC: 58010 AN: 151976 Hom.: 12080 Cov.: 32 AF XY: 0.385 AC XY: 28571 AN XY: 74276

African (AFR) AF: 0.554 AC: 22951 AN: 41450

American (AMR) AF: 0.285 AC: 4360 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1472 AN: 5166

South Asian (SAS) AF: 0.395 AC: 1906 AN: 4826

European-Finnish (FIN) AF: 0.401 AC: 4224 AN: 10522

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20907 AN: 67946

Other (OTH) AF: 0.350 AC: 737 AN: 2108

Alfa AF: 0.349 Hom.: 2161

Bravo AF: 0.377

Asia WGS AF: 0.357 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.36
PhyloP100		-0.065
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: rs9657894; hg19: chr7-150437927; COSMIC: COSV62280921; COSMIC: COSV62280921;