Variant 2-157542786-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_145259.3(ACVR1C):c.1020G>A(p.Ala340=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000969 in 1,613,994 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0036 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 25 hom. )

Consequence

ACVR1C
NM_145259.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.967

Variant links:

Genes affected

ACVR1C (HGNC:18123): (activin A receptor type 1C) ACVR1C is a type I receptor for the TGFB (see MIM 190180) family of signaling molecules. Upon ligand binding, type I receptors phosphorylate cytoplasmic SMAD transcription factors, which then translocate to the nucleus and interact directly with DNA or in complex with other transcription factors (Bondestam et al., 2001 [PubMed 12063393]).[supplied by OMIM, Mar 2008]

ACVR1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 2-157542786-C-T is Benign according to our data. Variant chr2-157542786-C-T is described in ClinVar as [Benign]. Clinvar id is 3039145.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.967 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00361 (549/152212) while in subpopulation AMR AF= 0.0348 (532/15294). AF 95% confidence interval is 0.0323. There are 18 homozygotes in gnomad4. There are 333 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 549 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ACVR1C	NM_145259.3 linkuse as main transcript	c.1020G>A	p.Ala340=	synonymous_variant	6/9	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2 linkuse as main transcript	c.870G>A	p.Ala290=	synonymous_variant	6/9		NP_001104501.1
ACVR1C	NM_001111032.2 linkuse as main transcript	c.780G>A	p.Ala260=	synonymous_variant	5/8		NP_001104502.1
ACVR1C	NM_001111033.2 linkuse as main transcript	c.549G>A	p.Ala183=	synonymous_variant	4/7		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13 linkuse as main transcript	c.1020G>A	p.Ala340=	synonymous_variant	6/9	1	NM_145259.3	ENSP00000243349	P1	Q8NER5-1
ACVR1C	ENST00000409680.7 linkuse as main transcript	c.870G>A	p.Ala290=	synonymous_variant	6/9	1		ENSP00000387168		Q8NER5-4
ACVR1C	ENST00000335450.7 linkuse as main transcript	c.780G>A	p.Ala260=	synonymous_variant	5/8	1		ENSP00000335178		Q8NER5-3
ACVR1C	ENST00000348328.9 linkuse as main transcript	c.549G>A	p.Ala183=	synonymous_variant	4/7	1		ENSP00000335139		Q8NER5-2

Frequencies

GnomAD3 genomes

AF:

0.00361

AC:

549

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0348

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00258

AC:

649

AN:

251384

Hom.:

AF XY:

0.00213

AC XY:

290

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000694

AC:

1015

AN:

1461782

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

450

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.000844

GnomAD4 genome

AF:

0.00361

AC:

549

AN:

152212

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0348

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000474

Hom.:

Bravo

AF:

0.00416

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ACVR1C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

6.9

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over