Genetic Variant ACVR1C:c.943+49G>A (chr2-157544396-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145259.3(ACVR1C):c.943+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,528,724 control chromosomes in the GnomAD database, including 502,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46329 hom., cov: 28)

Exomes 𝑓: 0.81 ( 455914 hom. )

Consequence

ACVR1C
NM_145259.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.914

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-157544396-C-T is Benign according to our data. Variant chr2-157544396-C-T is described in ClinVar as [Benign]. Clinvar id is 1287400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3 link	c.943+49G>A	intron_variant	Intron 5 of 8	ENST00000243349.13	NP_660302.2	Q8NER5-1
ACVR1C	NM_001111031.2 link	c.793+49G>A	intron_variant	Intron 5 of 8		NP_001104501.1	Q8NER5-4
ACVR1C	NM_001111032.2 link	c.703+49G>A	intron_variant	Intron 4 of 7		NP_001104502.1	Q8NER5-3
ACVR1C	NM_001111033.2 link	c.472+49G>A	intron_variant	Intron 3 of 6		NP_001104503.1	Q8NER5-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACVR1C	ENST00000243349.13 link	c.943+49G>A	intron_variant	Intron 5 of 8	1	NM_145259.3	ENSP00000243349.7	Q8NER5-1
ACVR1C	ENST00000409680.7 link	c.793+49G>A	intron_variant	Intron 5 of 8	1		ENSP00000387168.3	Q8NER5-4
ACVR1C	ENST00000335450.7 link	c.703+49G>A	intron_variant	Intron 4 of 7	1		ENSP00000335178.7	Q8NER5-3
ACVR1C	ENST00000348328.9 link	c.472+49G>A	intron_variant	Intron 3 of 6	1		ENSP00000335139.6	Q8NER5-2

Frequencies

GnomAD3 genomes

AF:

0.779

AC:

118105

AN:

151560

Hom.:

46296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.728

Gnomad AMR

AF:

0.788

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.921

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.822

Gnomad NFE

AF:

0.814

Gnomad OTH

AF:

0.795

GnomAD3 exomes

AF:

0.804

AC:

175990

AN:

218844

Hom.:

71069

AF XY:

0.804

AC XY:

95326

AN XY:

118520

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.797

Gnomad ASJ exome

AF:

0.778

Gnomad EAS exome

AF:

0.915

Gnomad SAS exome

AF:

0.759

Gnomad FIN exome

AF:

0.833

Gnomad NFE exome

AF:

0.813

Gnomad OTH exome

AF:

0.803

GnomAD4 exome

AF:

0.813

AC:

1119100

AN:

1377044

Hom.:

455914

Cov.:

AF XY:

0.811

AC XY:

556187

AN XY:

685410

show subpopulations

Gnomad4 AFR exome

AF:

0.679

Gnomad4 AMR exome

AF:

0.793

Gnomad4 ASJ exome

AF:

0.776

Gnomad4 EAS exome

AF:

0.933

Gnomad4 SAS exome

AF:

0.755

Gnomad4 FIN exome

AF:

0.831

Gnomad4 NFE exome

AF:

0.817

Gnomad4 OTH exome

AF:

0.811

GnomAD4 genome

AF:

0.779

AC:

118197

AN:

151680

Hom.:

46329

Cov.:

AF XY:

0.781

AC XY:

57892

AN XY:

74096

show subpopulations

Gnomad4 AFR

AF:

0.690

Gnomad4 AMR

AF:

0.788

Gnomad4 ASJ

AF:

0.770

Gnomad4 EAS

AF:

0.921

Gnomad4 SAS

AF:

0.765

Gnomad4 FIN

AF:

0.831

Gnomad4 NFE

AF:

0.814

Gnomad4 OTH

AF:

0.796

Alfa

AF:

0.793

Hom.:

15216

Bravo

AF:

0.775

Asia WGS

AF:

0.859

AC:

2984

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: 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

-0.89

CADD

Benign

0.23

DANN

Benign

0.62

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