rs6603979

Variant names:

• chr1-92513797-A-G
• rs6603979
• NM_001350197.2:c.2340T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-92513797-A-G
• chr1-92513797-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001350197.2(EVI5):​c.2340T>C​(p.Gly780Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 1,612,986 control chromosomes in the GnomAD database, including 547,967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55466 hom., cov: 26)
  • Exomes 𝑓: 0.82 (492501 hom.)
• Consequence: EVI5 NM_001350197.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00600

Genes affected

EVI5 (HGNC:3501): (ecotropic viral integration site 5) Enables GTPase activator activity and small GTPase binding activity. Involved in positive regulation of GTPase activity and retrograde transport, endosome to Golgi. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-92513797-A-G is Benign according to our data. Variant chr1-92513797-A-G is described in ClinVar as [Benign]. Clinvar id is 402836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.006 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVI5	NM_001350197.2	c.2340T>C	p.Gly780Gly	synonymous_variant	Exon 20 of 20	ENST00000684568.2	NP_001337126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVI5	ENST00000684568.2	c.2340T>C	p.Gly780Gly	synonymous_variant	Exon 20 of 20		NM_001350197.2	ENSP00000506999.1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129091 AN: 151390 Hom.: 55409 Cov.: 26

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.836

GnomAD2 exomes AF: 0.854 AC: 214425 AN: 251062 AF XY: 0.855

Gnomad AFR exome AF: 0.927

Gnomad AMR exome AF: 0.912

Gnomad ASJ exome AF: 0.881

Gnomad EAS exome AF: 0.965

Gnomad FIN exome AF: 0.778

Gnomad NFE exome AF: 0.795

Gnomad OTH exome AF: 0.837

GnomAD4 exome AF: 0.819 AC: 1196817 AN: 1461476 Hom.: 492501 Cov.: 47 AF XY: 0.823 AC XY: 598084 AN XY: 727060

African (AFR) AF: 0.932 AC: 31207 AN: 33476

American (AMR) AF: 0.909 AC: 40650 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 23059 AN: 26134

East Asian (EAS) AF: 0.974 AC: 38657 AN: 39698

South Asian (SAS) AF: 0.950 AC: 81943 AN: 86238

European-Finnish (FIN) AF: 0.775 AC: 41403 AN: 53404

Middle Eastern (MID) AF: 0.893 AC: 5148 AN: 5768

European-Non Finnish (NFE) AF: 0.795 AC: 884012 AN: 1111662

Other (OTH) AF: 0.840 AC: 50738 AN: 60384

GnomAD4 genome AF: 0.853 AC: 129211 AN: 151510 Hom.: 55466 Cov.: 26 AF XY: 0.856 AC XY: 63307 AN XY: 73994

African (AFR) AF: 0.929 AC: 38375 AN: 41302

American (AMR) AF: 0.869 AC: 13213 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3078 AN: 3468

East Asian (EAS) AF: 0.969 AC: 4983 AN: 5142

South Asian (SAS) AF: 0.952 AC: 4549 AN: 4776

European-Finnish (FIN) AF: 0.769 AC: 8037 AN: 10454

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54223 AN: 67870

Other (OTH) AF: 0.837 AC: 1757 AN: 2098

Alfa AF: 0.817 Hom.: 79158

Bravo AF: 0.861

Asia WGS AF: 0.954 AC: 3319 AN: 3478

EpiCase AF: 0.796

EpiControl AF: 0.802

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.51
PhyloP100		-0.0060
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

Publications

LitVar

Other links and lift over

dbSNP: rs6603979; hg19: chr1-92979354; COSMIC: COSV64828843;