1-92605315-C-G

Variant names:

• chr1-92605315-C-G
• rs1571845941
• NM_001350197.2:c.2062G>C

Variant summary

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

The NM_001350197.2(EVI5):​c.2062G>C​(p.Glu688Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EVI5 NM_001350197.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 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.2062G>C	p.Glu688Gln	missense	Exon 18 of 20	NP_001337126.1	A0A804HIC4
	EVI5	NM_001308248.2		c.2047G>C	p.Glu683Gln	missense	Exon 17 of 19	NP_001295177.1	O60447-2
	EVI5	NM_001377210.1		c.2038G>C	p.Glu680Gln	missense	Exon 17 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.2062G>C	p.Glu688Gln	missense	Exon 18 of 20	ENSP00000506999.1	A0A804HIC4
	EVI5	ENST00000540033.3	TSL:1	c.2047G>C	p.Glu683Gln	missense	Exon 17 of 19	ENSP00000440826.2	O60447-2
	EVI5	ENST00000370331.5	TSL:1	c.2014G>C	p.Glu672Gln	missense	Exon 16 of 18	ENSP00000359356.1	O60447-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455012 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724416

African (AFR) AF: 0.00 AC: 0 AN: 33316

American (AMR) AF: 0.00 AC: 0 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 85984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106218

Other (OTH) AF: 0.00 AC: 0 AN: 60144

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.17
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.061	T
Polyphen		0.99	D
Vest4		0.81
MutPred		0.14		Loss of loop (P = 0.1258)
MVP		0.64
MPC		0.46
ClinPred		0.96	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.58
Mutation Taster		=73/27	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: rs1571845941; hg19: chr1-93070872;