Genetic Variant EVA1C:p.Arg23Arg (chr21-32412920-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_058187.5(EVA1C):c.67C>A(p.Arg23Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,526,036 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 127 hom. )

Consequence

EVA1C
NM_058187.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.287

Publications

3 publications found

Variant links:

Genes affected

EVA1C (HGNC:13239): (eva-1 homolog C) Enables heparin binding activity. Colocalizes with extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

EVA1C links:

CFAP298-TCP10L (HGNC:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

CFAP298-TCP10L links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 21-32412920-C-A is Benign according to our data. Variant chr21-32412920-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2848841.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.287 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVA1C	NM_058187.5 link	c.67C>A	p.Arg23Arg	synonymous_variant	Exon 1 of 8	ENST00000300255.7	NP_478067.2	P58658-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVA1C	ENST00000300255.7 link	c.67C>A	p.Arg23Arg	synonymous_variant	Exon 1 of 8	1	NM_058187.5	ENSP00000300255.2		P58658-1

Frequencies

GnomAD3 genomes

AF:

0.00510

AC:

777

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0341

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00546

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.0106

AC:

1363

AN:

128130

AF XY:

0.00807

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.0485

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0262

Gnomad FIN exome

AF:

0.00390

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.00711

GnomAD4 exome

AF:

0.00298

AC:

4100

AN:

1373698

Hom.:

127

Cov.:

AF XY:

0.00278

AC XY:

1883

AN XY:

678366

show subpopulations

African (AFR)

AF:

0.000595

AC:

AN:

28554

American (AMR)

AF:

0.0474

AC:

1583

AN:

33380

Ashkenazi Jewish (ASJ)

AF:

0.0000409

AC:

AN:

24450

East Asian (EAS)

AF:

0.0568

AC:

1840

AN:

32368

South Asian (SAS)

AF:

0.000831

AC:

AN:

76996

European-Finnish (FIN)

AF:

0.00360

AC:

160

AN:

44480

Middle Eastern (MID)

AF:

0.000535

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

0.000191

AC:

204

AN:

1070858

Other (OTH)

AF:

0.00400

AC:

228

AN:

57004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

212

423

635

846

1058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00507

AC:

773

AN:

152338

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41594

American (AMR)

AF:

0.0282

AC:

432

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0342

AC:

176

AN:

5152

South Asian (SAS)

AF:

0.000827

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00546

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68024

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00727

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 22, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

7.0

(source)

DANN

Benign

0.91

PhyloP100

-0.29

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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21-32412920-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over