Genetic Variant ACVR1C:p.Ser450Ser (chr2-157538579-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_145259.3(ACVR1C):c.1350T>C(p.Ser450Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,560,074 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 3 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ACVR1C
NM_145259.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.25

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=-0.43).

BP6

Variant 2-157538579-A-G is Benign according to our data. Variant chr2-157538579-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 713452.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.25 with no splicing effect.

BS2

High AC in GnomAd4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3 link	c.1350T>C	p.Ser450Ser	synonymous_variant	Exon 8 of 9	ENST00000243349.13	NP_660302.2	Q8NER5-1
ACVR1C	NM_001111031.2 link	c.1200T>C	p.Ser400Ser	synonymous_variant	Exon 8 of 9		NP_001104501.1	Q8NER5-4
ACVR1C	NM_001111032.2 link	c.1110T>C	p.Ser370Ser	synonymous_variant	Exon 7 of 8		NP_001104502.1	Q8NER5-3
ACVR1C	NM_001111033.2 link	c.879T>C	p.Ser293Ser	synonymous_variant	Exon 6 of 7		NP_001104503.1	Q8NER5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACVR1C	ENST00000243349.13 link	c.1350T>C	p.Ser450Ser	synonymous_variant	Exon 8 of 9	1	NM_145259.3	ENSP00000243349.7	Q8NER5-1
ACVR1C	ENST00000409680.7 link	c.1200T>C	p.Ser400Ser	synonymous_variant	Exon 8 of 9	1		ENSP00000387168.3	Q8NER5-4
ACVR1C	ENST00000335450.7 link	c.1110T>C	p.Ser370Ser	synonymous_variant	Exon 7 of 8	1		ENSP00000335178.7	Q8NER5-3
ACVR1C	ENST00000348328.9 link	c.879T>C	p.Ser293Ser	synonymous_variant	Exon 6 of 7	1		ENSP00000335139.6	Q8NER5-2

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00000458

AC:

AN:

218126

Hom.:

AF XY:

0.00

AC XY:

AN XY:

118334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000201

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1407736

Hom.:

Cov.:

AF XY:

0.0000215

AC XY:

AN XY:

698574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000466

GnomAD4 genome

AF:

0.000243

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00473

Bravo

AF:

0.0000567

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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

-0.43

CADD

Benign

DANN

Benign

0.69

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