rs2391199

Variant names:

• chr1-92695345-T-C
• rs2391199
• NM_001350197.2:c.874A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-92695345-T-C
• chr1-92695345-T-A
• chr1-92695345-T-G

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.874A>G​(p.Ile292Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,610,852 control chromosomes in the GnomAD database, including 669,658 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64680 hom., cov: 31)
  • Exomes 𝑓: 0.91 (604978 hom.)
• Consequence: EVI5 NM_001350197.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.141
• Publications: 39 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=1.796969E-6).
• BP6: Variant 1-92695345-T-C is Benign according to our data. Variant chr1-92695345-T-C is described in ClinVar as Benign. ClinVar VariationId is 402839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 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.874A>G	p.Ile292Val	missense	Exon 7 of 20	NP_001337126.1	A0A804HIC4
	EVI5	NM_001308248.2		c.1006A>G	p.Ile336Val	missense	Exon 7 of 19	NP_001295177.1	O60447-2
	EVI5	NM_001377210.1		c.997A>G	p.Ile333Val	missense	Exon 7 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.874A>G	p.Ile292Val	missense	Exon 7 of 20	ENSP00000506999.1	A0A804HIC4
	EVI5	ENST00000540033.3	TSL:1	c.1006A>G	p.Ile336Val	missense	Exon 7 of 19	ENSP00000440826.2	O60447-2
	EVI5	ENST00000370331.5	TSL:1	c.1006A>G	p.Ile336Val	missense	Exon 7 of 18	ENSP00000359356.1	O60447-1

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140112 AN: 152086 Hom.: 64629 Cov.: 31

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.912

GnomAD2 exomes AF: 0.924 AC: 231570 AN: 250646 AF XY: 0.924

Gnomad AFR exome AF: 0.943

Gnomad AMR exome AF: 0.955

Gnomad ASJ exome AF: 0.955

Gnomad EAS exome AF: 0.965

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.898

Gnomad OTH exome AF: 0.920

GnomAD4 exome AF: 0.910 AC: 1327783 AN: 1458648 Hom.: 604978 Cov.: 31 AF XY: 0.912 AC XY: 661948 AN XY: 725820

African (AFR) AF: 0.946 AC: 31595 AN: 33412

American (AMR) AF: 0.952 AC: 42422 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 24913 AN: 26090

East Asian (EAS) AF: 0.974 AC: 38622 AN: 39654

South Asian (SAS) AF: 0.968 AC: 83282 AN: 86000

European-Finnish (FIN) AF: 0.884 AC: 47166 AN: 53380

Middle Eastern (MID) AF: 0.960 AC: 5527 AN: 5758

European-Non Finnish (NFE) AF: 0.900 AC: 998810 AN: 1109540

Other (OTH) AF: 0.920 AC: 55446 AN: 60276

GnomAD4 genome AF: 0.921 AC: 140223 AN: 152204 Hom.: 64680 Cov.: 31 AF XY: 0.922 AC XY: 68629 AN XY: 74406

African (AFR) AF: 0.945 AC: 39251 AN: 41540

American (AMR) AF: 0.934 AC: 14279 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3334 AN: 3470

East Asian (EAS) AF: 0.969 AC: 5020 AN: 5182

South Asian (SAS) AF: 0.967 AC: 4663 AN: 4822

European-Finnish (FIN) AF: 0.884 AC: 9340 AN: 10570

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61265 AN: 68014

Other (OTH) AF: 0.912 AC: 1926 AN: 2112

Alfa AF: 0.908 Hom.: 269765

Bravo AF: 0.924

TwinsUK AF: 0.898 AC: 3328

ALSPAC AF: 0.898 AC: 3459

ESP6500AA AF: 0.942 AC: 4151

ESP6500EA AF: 0.898 AC: 7723

ExAC AF: 0.922 AC: 111891

Asia WGS AF: 0.963 AC: 3350 AN: 3478

EpiCase AF: 0.904

EpiControl AF: 0.903

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
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.8
DANN	Benign	0.80
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.12	N
PhyloP100		-0.14
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.058
Sift	Benign	0.61	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.071
MPC		0.13
ClinPred		0.00043	T
GERP RS		2.3
Varity_R		0.039
gMVP		0.13
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2391199; hg19: chr1-93160902; COSMIC: COSV107463201;