chr7-150737602-G-A

Variant names:

• chr7-150737602-G-A
• rs193233179
• ENST00000611999.4:c.500G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001199577.2(GIMAP1-GIMAP5):​c.500G>A​(p.Arg167His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,535,618 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0054 (28 hom.)
• Consequence: GIMAP1-GIMAP5 NM_001199577.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040815473).
• BP6: Variant 7-150737602-G-A is Benign according to our data. Variant chr7-150737602-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3387861.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.-113G>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.500G>A	p.Arg167His	missense_variant	Exon 4 of 6		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.116G>A	p.Arg39His	missense_variant	Exon 3 of 5		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP1-GIMAP5	ENST00000611999.4	c.500G>A	p.Arg167His	missense_variant	Exon 4 of 6	5		ENSP00000477920.1
GIMAP5	ENST00000358647	c.-113G>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_018384.5	ENSP00000351473.3

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 493 AN: 152146 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00548

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00283 AC: 367 AN: 129566 Hom.: 1 AF XY: 0.00295 AC XY: 209 AN XY: 70832

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00103

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000983

Gnomad FIN exome AF: 0.00223

Gnomad NFE exome AF: 0.00590

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00540 AC: 7476 AN: 1383354 Hom.: 28 Cov.: 31 AF XY: 0.00517 AC XY: 3526 AN XY: 682576

Gnomad4 AFR exome AF: 0.000981

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000896

Gnomad4 FIN exome AF: 0.00200

Gnomad4 NFE exome AF: 0.00649

Gnomad4 OTH exome AF: 0.00402

GnomAD4 genome AF: 0.00324 AC: 493 AN: 152264 Hom.: 1 Cov.: 31 AF XY: 0.00304 AC XY: 226 AN XY: 74450

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00548

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00337 Hom.: 0

Bravo AF: 0.00328

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00571 AC: 22

ExAC AF: 0.00111 AC: 19

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GIMAP1-GIMAP5: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.2
DANN	Benign	0.81
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0041	T
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.15	T
Vest4		0.058
MVP		0.061
GERP RS		-3.0
gMVP		0.68

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: rs193233179; hg19: chr7-150434690;