rs11808092

chr1-92607671-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001350197.2(EVI5):c.1884G>T(p.Gln628His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,603,890 control chromosomes in the GnomAD database, including 45,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3454 hom., cov: 31)
  • Exomes 𝑓: 0.23 (42127 hom.)
• Consequence: EVI5 NM_001350197.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.721

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014106333).
• BP6: Variant 1-92607671-C-A is Benign according to our data. Variant chr1-92607671-C-A is described in ClinVar as [Benign]. Clinvar id is 402837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVI5	NM_001350197.2	c.1884G>T	p.Gln628His	missense_variant	17/20	ENST00000684568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVI5	ENST00000684568.2	c.1884G>T	p.Gln628His	missense_variant	17/20		NM_001350197.2	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29697 AN: 151808 Hom.: 3454 Cov.: 31

Gnomad AFR AF: 0.0945

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.234

GnomAD3 exomes AF: 0.195 AC: 47734 AN: 244648 Hom.: 5390 AF XY: 0.197 AC XY: 25994 AN XY: 132264

Gnomad AFR exome AF: 0.0892

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.0217

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.233 AC: 337719 AN: 1451964 Hom.: 42127 Cov.: 28 AF XY: 0.230 AC XY: 166281 AN XY: 722290

Gnomad4 AFR exome AF: 0.0895

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.0174

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.196 AC: 29711 AN: 151926 Hom.: 3454 Cov.: 31 AF XY: 0.194 AC XY: 14423 AN XY: 74218

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.230

Alfa AF: 0.240 Hom.: 11469

Bravo AF: 0.187

TwinsUK AF: 0.261 AC: 969

ALSPAC AF: 0.256 AC: 988

ESP6500AA AF: 0.106 AC: 467

ESP6500EA AF: 0.257 AC: 2206

ExAC AF: 0.194 AC: 23595

Asia WGS AF: 0.0830 AC: 291 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;D
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	0.00017	P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.11
Sift	Benign	0.049	D;.
Sift4G	Uncertain	0.049	D;D
Polyphen		0.0030	B;.
Vest4		0.10
MutPred		0.18		.;Loss of ubiquitination at K625 (P = 0.091);
MPC		0.14
ClinPred		0.032	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.34

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: rs11808092; hg19: chr1-93073228; COSMIC: COSV64830581;