ENST00000611999.4:c.403-121G>A

Variant names:

• chr7-150737384-G-A
• rs6965571
• ENST00000611999.4:c.403-121G>A

Variant summary

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

The ENST00000611999.4(GIMAP1-GIMAP5):​c.403-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 715,118 control chromosomes in the GnomAD database, including 9,532 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 0.17 (2453 hom., cov: 31)
  • Exomes 𝑓: 0.15 (7079 hom.)
• Consequence: GIMAP1-GIMAP5 ENST00000611999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 23 publications found

Genes affected

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: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]

GIMAP5 Gene-Disease associations (from GenCC):

• portal hypertension, noncirrhotic, 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP1-GIMAP5	NM_001199577.2	c.403-121G>A		intron_variant	Intron 3 of 5		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.19-121G>A		intron_variant	Intron 2 of 4		NP_001290559.1
GIMAP5	NM_018384.5	c.-331G>A		upstream_gene_variant		ENST00000358647.5	NP_060854.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP1-GIMAP5	ENST00000611999.4	c.403-121G>A		intron_variant	Intron 3 of 5	5		ENSP00000477920.1
GIMAP5	ENST00000358647.5	c.-331G>A		upstream_gene_variant		1	NM_018384.5	ENSP00000351473.3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26277 AN: 151388 Hom.: 2451 Cov.: 31

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.151 AC: 85387 AN: 563670 Hom.: 7079 Cov.: 7 AF XY: 0.151 AC XY: 44520 AN XY: 295424

African (AFR) AF: 0.230 AC: 3621 AN: 15722

American (AMR) AF: 0.108 AC: 3277 AN: 30360

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 2960 AN: 16378

East Asian (EAS) AF: 0.00631 AC: 201 AN: 31838

South Asian (SAS) AF: 0.115 AC: 6068 AN: 52912

European-Finnish (FIN) AF: 0.132 AC: 4048 AN: 30720

Middle Eastern (MID) AF: 0.194 AC: 511 AN: 2630

European-Non Finnish (NFE) AF: 0.170 AC: 60033 AN: 352692

Other (OTH) AF: 0.153 AC: 4668 AN: 30418

GnomAD4 genome AF: 0.174 AC: 26292 AN: 151448 Hom.: 2453 Cov.: 31 AF XY: 0.170 AC XY: 12532 AN XY: 73894

African (AFR) AF: 0.227 AC: 9338 AN: 41226

American (AMR) AF: 0.140 AC: 2136 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3468

East Asian (EAS) AF: 0.0117 AC: 60 AN: 5138

South Asian (SAS) AF: 0.112 AC: 537 AN: 4796

European-Finnish (FIN) AF: 0.128 AC: 1329 AN: 10376

Middle Eastern (MID) AF: 0.243 AC: 70 AN: 288

European-Non Finnish (NFE) AF: 0.173 AC: 11735 AN: 67914

Other (OTH) AF: 0.176 AC: 367 AN: 2090

Alfa AF: 0.174 Hom.: 10051

Bravo AF: 0.175

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		-2.7
PromoterAI		-0.034	Neutral
Mutation Taster		=300/0	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: rs6965571; hg19: chr7-150434472;