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
• Publications: 22 publications found

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	NM_001350197.2	MANE Select	c.2340T>C	p.Gly780Gly	synonymous	Exon 20 of 20	NP_001337126.1	A0A804HIC4
	EVI5	NM_001308248.2		c.2325T>C	p.Gly775Gly	synonymous	Exon 19 of 19	NP_001295177.1	O60447-2
	EVI5	NM_001377210.1		c.2316T>C	p.Gly772Gly	synonymous	Exon 19 of 19	NP_001364139.1	A0A9L9PXL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	ENST00000684568.2	MANE Select	c.2340T>C	p.Gly780Gly	synonymous	Exon 20 of 20	ENSP00000506999.1	A0A804HIC4
	EVI5	ENST00000540033.3	TSL:1	c.2325T>C	p.Gly775Gly	synonymous	Exon 19 of 19	ENSP00000440826.2	O60447-2
	EVI5	ENST00000370331.5	TSL:1	c.2292T>C	p.Gly764Gly	synonymous	Exon 18 of 18	ENSP00000359356.1	O60447-1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Other links and lift over

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