chr2-75493246-C-T

Variant names:

• chr2-75493246-C-T
• rs11126472
• NM_001135032.2:c.449G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001135032.2(EVA1A):​c.449G>A​(p.Arg150His) variant causes a missense change. The variant allele was found at a frequency of 0.0469 in 1,611,076 control chromosomes in the GnomAD database, including 2,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.052 (245 hom., cov: 33)
  • Exomes 𝑓: 0.046 (1794 hom.)
• Consequence: EVA1A NM_001135032.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.07
• Publications: 12 publications found

Genes affected

EVA1A (HGNC:25816): (eva-1 homolog A, regulator of programmed cell death) Predicted to be involved in apoptotic process and autophagy. Located in intracellular membrane-bounded organelle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016549826).
• BP6: Variant 2-75493246-C-T is Benign according to our data. Variant chr2-75493246-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056113.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135032.2. 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
	EVA1A	NM_001135032.2	MANE Select	c.449G>A	p.Arg150His	missense	Exon 4 of 4	NP_001128504.1	Q9H8M9
	EVA1A	NM_001369524.1		c.449G>A	p.Arg150His	missense	Exon 6 of 6	NP_001356453.1	Q9H8M9
	EVA1A	NM_001369525.1		c.449G>A	p.Arg150His	missense	Exon 5 of 5	NP_001356454.1	Q9H8M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1A	ENST00000393913.8	TSL:1 MANE Select	c.449G>A	p.Arg150His	missense	Exon 4 of 4	ENSP00000377490.3	Q9H8M9
	EVA1A	ENST00000910300.1		c.506G>A	p.Arg169His	missense	Exon 4 of 4	ENSP00000580359.1
	EVA1A	ENST00000910305.1		c.506G>A	p.Arg169His	missense	Exon 3 of 3	ENSP00000580364.1

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7860 AN: 152182 Hom.: 245 Cov.: 33

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.0390

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0588

GnomAD2 exomes AF: 0.0412 AC: 10143 AN: 246392 AF XY: 0.0425

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.0233

Gnomad ASJ exome AF: 0.0580

Gnomad EAS exome AF: 0.000437

Gnomad FIN exome AF: 0.0234

Gnomad NFE exome AF: 0.0523

Gnomad OTH exome AF: 0.0497

GnomAD4 exome AF: 0.0464 AC: 67723 AN: 1458776 Hom.: 1794 Cov.: 30 AF XY: 0.0464 AC XY: 33636 AN XY: 725410

African (AFR) AF: 0.0713 AC: 2385 AN: 33438

American (AMR) AF: 0.0245 AC: 1092 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 1560 AN: 25932

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39692

South Asian (SAS) AF: 0.0379 AC: 3255 AN: 85840

European-Finnish (FIN) AF: 0.0236 AC: 1255 AN: 53088

Middle Eastern (MID) AF: 0.0975 AC: 533 AN: 5468

European-Non Finnish (NFE) AF: 0.0494 AC: 54823 AN: 1110474

Other (OTH) AF: 0.0466 AC: 2806 AN: 60266

GnomAD4 genome AF: 0.0517 AC: 7867 AN: 152300 Hom.: 245 Cov.: 33 AF XY: 0.0491 AC XY: 3660 AN XY: 74470

African (AFR) AF: 0.0680 AC: 2828 AN: 41560

American (AMR) AF: 0.0391 AC: 598 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0406 AC: 196 AN: 4828

European-Finnish (FIN) AF: 0.0200 AC: 212 AN: 10612

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0508 AC: 3456 AN: 68018

Other (OTH) AF: 0.0587 AC: 124 AN: 2114

Alfa AF: 0.0508 Hom.: 673

Bravo AF: 0.0539

TwinsUK AF: 0.0472 AC: 175

ALSPAC AF: 0.0501 AC: 193

ESP6500AA AF: 0.0640 AC: 281

ESP6500EA AF: 0.0509 AC: 437

ExAC AF: 0.0438 AC: 5310

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EVA1A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0034	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.23
MPC		1.3
ClinPred		0.027	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.58
Mutation Taster		=99/1	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: rs11126472; hg19: chr2-75720372; COSMIC: COSV52060745; COSMIC: COSV52060745;