rs770316787

Variant names:

• chr1-92607606-C-T
• rs770316787
• NM_001350197.2:c.1949G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001350197.2(EVI5):​c.1949G>A​(p.Arg650His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,592,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: EVI5 NM_001350197.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1949G>A	p.Arg650His	missense	Exon 17 of 20	NP_001337126.1	A0A804HIC4
	EVI5	NM_001308248.2		c.1934G>A	p.Arg645His	missense	Exon 16 of 19	NP_001295177.1	O60447-2
	EVI5	NM_001377210.1		c.1925G>A	p.Arg642His	missense	Exon 16 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.1949G>A	p.Arg650His	missense	Exon 17 of 20	ENSP00000506999.1	A0A804HIC4
	EVI5	ENST00000540033.3	TSL:1	c.1934G>A	p.Arg645His	missense	Exon 16 of 19	ENSP00000440826.2	O60447-2
	EVI5	ENST00000370331.5	TSL:1	c.1901G>A	p.Arg634His	missense	Exon 15 of 18	ENSP00000359356.1	O60447-1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000347 AC: 8 AN: 230722 AF XY: 0.0000641

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000175

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000927

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000299 AC: 43 AN: 1440098 Hom.: 0 Cov.: 29 AF XY: 0.0000335 AC XY: 24 AN XY: 715622

African (AFR) AF: 0.0000311 AC: 1 AN: 32190

American (AMR) AF: 0.000126 AC: 5 AN: 39646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25566

East Asian (EAS) AF: 0.0000771 AC: 3 AN: 38906

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80912

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.0000281 AC: 31 AN: 1105108

Other (OTH) AF: 0.0000168 AC: 1 AN: 59692

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74248

African (AFR) AF: 0.0000242 AC: 1 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000284 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.37	T
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.24		Loss of MoRF binding (P = 0.0205)
MVP		0.56
MPC		0.68
ClinPred		0.55	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.40
Mutation Taster		=57/43	polymorphism

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: rs770316787; hg19: chr1-93073163; COSMIC: COSV64826759; COSMIC: COSV64826759;