rs762173

Variant names:

• chr21-32460367-A-G
• rs762173
• NM_058187.5:c.481+2647A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_058187.5(EVA1C):​c.481+2647A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,980 control chromosomes in the GnomAD database, including 14,422 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14422 hom., cov: 32)
• Consequence: EVA1C NM_058187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57
• Publications: 5 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058187.5. 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
	EVA1C	NM_058187.5	MANE Select	c.481+2647A>G		intron	N/A	NP_478067.2
	EVA1C	NM_001286556.2		c.481+2647A>G		intron	N/A	NP_001273485.1	P58658-3
	EVA1C	NM_001320745.2		c.196+2647A>G		intron	N/A	NP_001307674.1	B3KWG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1C	ENST00000300255.7	TSL:1 MANE Select	c.481+2647A>G		intron	N/A	ENSP00000300255.2	P58658-1
	EVA1C	ENST00000382699.7	TSL:1	c.481+2647A>G		intron	N/A	ENSP00000372146.3	P58658-3
	EVA1C	ENST00000437338.5	TSL:1	n.*71+2647A>G		intron	N/A	ENSP00000389291.1	A0A0C4DG64

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64608 AN: 151862 Hom.: 14385 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64687 AN: 151980 Hom.: 14422 Cov.: 32 AF XY: 0.426 AC XY: 31664 AN XY: 74268

African (AFR) AF: 0.533 AC: 22075 AN: 41454

American (AMR) AF: 0.498 AC: 7616 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3468

East Asian (EAS) AF: 0.527 AC: 2715 AN: 5156

South Asian (SAS) AF: 0.420 AC: 2023 AN: 4816

European-Finnish (FIN) AF: 0.293 AC: 3082 AN: 10526

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24631 AN: 67966

Other (OTH) AF: 0.407 AC: 858 AN: 2108

Alfa AF: 0.387 Hom.: 40552

Bravo AF: 0.446

Asia WGS AF: 0.442 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.26
PhyloP100		-3.6
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs762173;

hg19: chr21-33832675;