7-150742952-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_018384.5(GIMAP5):c.813G>A(p.Ala271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,614,206 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (12 hom.)
• Consequence: GIMAP5 NM_018384.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.254

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:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-150742952-G-A is Benign according to our data. Variant chr7-150742952-G-A is described in ClinVar as [Benign]. Clinvar id is 776271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.254 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00798 (1215/152314) while in subpopulation AFR AF= 0.0277 (1149/41554). AF 95% confidence interval is 0.0263. There are 12 homozygotes in gnomad4. There are 572 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIMAP5	NM_018384.5	c.813G>A	p.Ala271=	synonymous_variant	3/3	ENST00000358647.5
GIMAP1-GIMAP5	NM_001199577.2	c.1425G>A	p.Ala475=	synonymous_variant	6/6
GIMAP1-GIMAP5	NM_001303630.2	c.1041G>A	p.Ala347=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIMAP5	ENST00000358647.5	c.813G>A	p.Ala271=	synonymous_variant	3/3	1	NM_018384.5	P1

Frequencies

GnomAD3 genomes AF: 0.00796 AC: 1211 AN: 152196 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00197 AC: 496 AN: 251244 Hom.: 6 AF XY: 0.00129 AC XY: 175 AN XY: 135810

Gnomad AFR exome AF: 0.0272

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000805 AC: 1177 AN: 1461892 Hom.: 12 Cov.: 65 AF XY: 0.000686 AC XY: 499 AN XY: 727248

Gnomad4 AFR exome AF: 0.0290

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00156

GnomAD4 genome AF: 0.00798 AC: 1215 AN: 152314 Hom.: 12 Cov.: 32 AF XY: 0.00768 AC XY: 572 AN XY: 74474

Gnomad4 AFR AF: 0.0277

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00445 Hom.: 6

Bravo AF: 0.00943

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.4
Dann	Benign	0.65

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: rs61751050; hg19: chr7-150440040; COSMIC: COSV100500310; COSMIC: COSV100500310;