rs11808092

Variant names:

• chr1-92607671-C-A
• rs11808092
• NM_001350197.2:c.1884G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q628R) has been classified as Uncertain significance.

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.721
• Publications: 35 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 -20 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 VariationId is 402837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	NM_001350197.2	MANE Select	c.1884G>T	p.Gln628His	missense	Exon 17 of 20	NP_001337126.1
	EVI5	NM_001308248.2		c.1869G>T	p.Gln623His	missense	Exon 16 of 19	NP_001295177.1
	EVI5	NM_001377210.1		c.1860G>T	p.Gln620His	missense	Exon 16 of 19	NP_001364139.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	ENST00000684568.2	MANE Select	c.1884G>T	p.Gln628His	missense	Exon 17 of 20	ENSP00000506999.1
	EVI5	ENST00000540033.3	TSL:1	c.1869G>T	p.Gln623His	missense	Exon 16 of 19	ENSP00000440826.2
	EVI5	ENST00000370331.5	TSL:1	c.1836G>T	p.Gln612His	missense	Exon 15 of 18	ENSP00000359356.1

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

GnomAD2 exomes AF: 0.195 AC: 47734 AN: 244648 AF XY: 0.197

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 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

African (AFR) AF: 0.0895 AC: 2967 AN: 33160

American (AMR) AF: 0.172 AC: 7482 AN: 43626

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 7347 AN: 25960

East Asian (EAS) AF: 0.0174 AC: 686 AN: 39518

South Asian (SAS) AF: 0.120 AC: 10132 AN: 84694

European-Finnish (FIN) AF: 0.241 AC: 12689 AN: 52696

Middle Eastern (MID) AF: 0.240 AC: 1382 AN: 5750

European-Non Finnish (NFE) AF: 0.254 AC: 281422 AN: 1106490

Other (OTH) AF: 0.227 AC: 13612 AN: 60070

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

African (AFR) AF: 0.0945 AC: 3919 AN: 41474

American (AMR) AF: 0.222 AC: 3390 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 945 AN: 3464

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5176

South Asian (SAS) AF: 0.120 AC: 578 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2701 AN: 10516

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17322 AN: 67926

Other (OTH) AF: 0.230 AC: 486 AN: 2110

Alfa AF: 0.234 Hom.: 19963

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

ClinVar submissions as Germline

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
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
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.72
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Benign	0.049	D
Sift4G	Uncertain	0.049	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
Mutation Taster		=95/5	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: rs11808092; hg19: chr1-93073228; COSMIC: COSV64830581;