Variant 2-157544441-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_145259.3(ACVR1C):c.943+4T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000781 in 1,605,248 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00081 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00078 ( 9 hom. )

Consequence

ACVR1C
NM_145259.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.0001835

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.682

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 2-157544441-A-G is Benign according to our data. Variant chr2-157544441-A-G is described in ClinVar as [Benign]. Clinvar id is 3039871.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ACVR1C	NM_145259.3 linkuse as main transcript	c.943+4T>C	splice_donor_region_variant, intron_variant	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2 linkuse as main transcript	c.793+4T>C	splice_donor_region_variant, intron_variant		NP_001104501.1
ACVR1C	NM_001111032.2 linkuse as main transcript	c.703+4T>C	splice_donor_region_variant, intron_variant		NP_001104502.1
ACVR1C	NM_001111033.2 linkuse as main transcript	c.472+4T>C	splice_donor_region_variant, intron_variant		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13 linkuse as main transcript	c.943+4T>C	splice_donor_region_variant, intron_variant	1	NM_145259.3	ENSP00000243349	P1	Q8NER5-1
ACVR1C	ENST00000335450.7 linkuse as main transcript	c.703+4T>C	splice_donor_region_variant, intron_variant	1		ENSP00000335178		Q8NER5-3
ACVR1C	ENST00000348328.9 linkuse as main transcript	c.472+4T>C	splice_donor_region_variant, intron_variant	1		ENSP00000335139		Q8NER5-2
ACVR1C	ENST00000409680.7 linkuse as main transcript	c.793+4T>C	splice_donor_region_variant, intron_variant	1		ENSP00000387168		Q8NER5-4

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00141

AC:

344

AN:

243930

Hom.:

AF XY:

0.00142

AC XY:

187

AN XY:

131598

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.000153

Gnomad ASJ exome

AF:

0.0305

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000323

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.000778

AC:

1130

AN:

1452978

Hom.:

Cov.:

AF XY:

0.000797

AC XY:

576

AN XY:

722438

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.0309

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.000814

AC:

124

AN:

152270

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00242

Hom.:

Bravo

AF:

0.000937

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

Sep 17, 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

-0.69

CADD

Benign

0.34

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.012

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