21-32495163-C-T

Variant names:

• chr21-32495163-C-T
• rs61739732
• NM_058187.5:c.771C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_058187.5(EVA1C):​c.771C>T​(p.Tyr257Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,613,986 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (72 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (64 hom.)
• Consequence: EVA1C NM_058187.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60
• Publications: 0 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 21-32495163-C-T is Benign according to our data. Variant chr21-32495163-C-T is described in ClinVar as Benign. ClinVar VariationId is 787504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 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.771C>T	p.Tyr257Tyr	synonymous	Exon 5 of 8	NP_478067.2
	EVA1C	NM_001286556.2		c.771C>T	p.Tyr257Tyr	synonymous	Exon 5 of 8	NP_001273485.1	P58658-3
	EVA1C	NM_001320745.2		c.486C>T	p.Tyr162Tyr	synonymous	Exon 5 of 8	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.771C>T	p.Tyr257Tyr	synonymous	Exon 5 of 8	ENSP00000300255.2	P58658-1
	EVA1C	ENST00000382699.7	TSL:1	c.771C>T	p.Tyr257Tyr	synonymous	Exon 5 of 8	ENSP00000372146.3	P58658-3
	EVA1C	ENST00000437338.5	TSL:1	n.*361C>T		non_coding_transcript_exon	Exon 4 of 7	ENSP00000389291.1	A0A0C4DG64

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2439 AN: 152124 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00412 AC: 1036 AN: 251354 AF XY: 0.00299

Gnomad AFR exome AF: 0.0560

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00170 AC: 2490 AN: 1461744 Hom.: 64 Cov.: 31 AF XY: 0.00148 AC XY: 1073 AN XY: 727174

African (AFR) AF: 0.0563 AC: 1885 AN: 33474

American (AMR) AF: 0.00322 AC: 144 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26120

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39696

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00419 AC: 24 AN: 5730

European-Non Finnish (NFE) AF: 0.000147 AC: 163 AN: 1111958

Other (OTH) AF: 0.00421 AC: 254 AN: 60382

GnomAD4 genome AF: 0.0161 AC: 2456 AN: 152242 Hom.: 72 Cov.: 32 AF XY: 0.0160 AC XY: 1194 AN XY: 74446

African (AFR) AF: 0.0553 AC: 2295 AN: 41518

American (AMR) AF: 0.00732 AC: 112 AN: 15296

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

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68026

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00715 Hom.: 16

Bravo AF: 0.0189

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	6.9
DANN	Benign	0.93
PhyloP100		-1.6
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs61739732; hg19: chr21-33867473;