1-92624266-T-C

Variant names:

• chr1-92624266-T-C
• rs7514716
• NM_001350197.2:c.1737A>G

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.1737A>G​(p.Gln579Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,612,592 control chromosomes in the GnomAD database, including 669,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64653 hom., cov: 30)
  • Exomes 𝑓: 0.91 (605108 hom.)
• Consequence: EVI5 NM_001350197.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.851
• Publications: 23 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=-0.52).
• BP6: Variant 1-92624266-T-C is Benign according to our data. Variant chr1-92624266-T-C is described in ClinVar as Benign. ClinVar VariationId is 402838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.851 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVI5	NM_001350197.2	c.1737A>G	p.Gln579Gln	synonymous_variant	Exon 16 of 20	ENST00000684568.2	NP_001337126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVI5	ENST00000684568.2	c.1737A>G	p.Gln579Gln	synonymous_variant	Exon 16 of 20		NM_001350197.2	ENSP00000506999.1

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140048 AN: 152016 Hom.: 64602 Cov.: 30

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.936

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.912

GnomAD2 exomes AF: 0.924 AC: 232199 AN: 251348 AF XY: 0.924

Gnomad AFR exome AF: 0.944

Gnomad AMR exome AF: 0.955

Gnomad ASJ exome AF: 0.953

Gnomad EAS exome AF: 0.965

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.898

Gnomad OTH exome AF: 0.919

GnomAD4 exome AF: 0.910 AC: 1328745 AN: 1460458 Hom.: 605108 Cov.: 35 AF XY: 0.912 AC XY: 662373 AN XY: 726638

African (AFR) AF: 0.947 AC: 31671 AN: 33460

American (AMR) AF: 0.953 AC: 42596 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 24923 AN: 26126

East Asian (EAS) AF: 0.974 AC: 38644 AN: 39674

South Asian (SAS) AF: 0.968 AC: 83511 AN: 86240

European-Finnish (FIN) AF: 0.883 AC: 47175 AN: 53400

Middle Eastern (MID) AF: 0.960 AC: 5529 AN: 5760

European-Non Finnish (NFE) AF: 0.900 AC: 999196 AN: 1110726

Other (OTH) AF: 0.920 AC: 55500 AN: 60354

GnomAD4 genome AF: 0.921 AC: 140159 AN: 152134 Hom.: 64653 Cov.: 30 AF XY: 0.922 AC XY: 68600 AN XY: 74368

African (AFR) AF: 0.946 AC: 39243 AN: 41498

American (AMR) AF: 0.934 AC: 14271 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3329 AN: 3472

East Asian (EAS) AF: 0.969 AC: 5001 AN: 5162

South Asian (SAS) AF: 0.967 AC: 4657 AN: 4816

European-Finnish (FIN) AF: 0.884 AC: 9350 AN: 10582

Middle Eastern (MID) AF: 0.932 AC: 272 AN: 292

European-Non Finnish (NFE) AF: 0.900 AC: 61247 AN: 68018

Other (OTH) AF: 0.912 AC: 1918 AN: 2102

Alfa AF: 0.910 Hom.: 110947

Bravo AF: 0.924

Asia WGS AF: 0.963 AC: 3351 AN: 3478

EpiCase AF: 0.904

EpiControl AF: 0.902

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	-0.52
CADD	Benign	6.8
DANN	Benign	0.64
PhyloP100		0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7514716; hg19: chr1-93089823; COSMIC: COSV108213988; COSMIC: COSV108213988;