ENST00000476324.1:n.4762A>G

Variant names:

• chr7-150743626-A-G
• rs2286899
• ENST00000476324.1:n.4762A>G

Variant summary

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

The ENST00000476324.1(GIMAP5):​n.4762A>G 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 0.134 in 152,390 control chromosomes in the GnomAD database, including 1,666 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 0.13 (1666 hom., cov: 32)
  • Exomes 𝑓: 0.088 (0 hom.)
• Consequence: GIMAP5 ENST00000476324.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) 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.*563A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.*563A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.*563A>G		3_prime_UTR_variant	Exon 5 of 5		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.*563A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.*563A>G		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000477920.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20387 AN: 152090 Hom.: 1668 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0879 AC: 16 AN: 182 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 6 AN XY: 96

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0882 AC: 15 AN: 170

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.134 AC: 20417 AN: 152208 Hom.: 1666 Cov.: 32 AF XY: 0.141 AC XY: 10504 AN XY: 74408

African (AFR) AF: 0.0838 AC: 3481 AN: 41550

American (AMR) AF: 0.120 AC: 1831 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 491 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1347 AN: 5174

South Asian (SAS) AF: 0.134 AC: 648 AN: 4826

European-Finnish (FIN) AF: 0.273 AC: 2889 AN: 10566

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9352 AN: 68006

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.126 Hom.: 844

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.47
PhyloP100		0.77
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: rs2286899; hg19: chr7-150440714;