chr2-157544593-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_145259.3(ACVR1C):c.795A>G(p.Gln265Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,611,678 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 56 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 51 hom. )

Consequence

ACVR1C
NM_145259.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.222

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-157544593-T-C is Benign according to our data. Variant chr2-157544593-T-C is described in ClinVar as Benign. ClinVar VariationId is 783343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.222 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2142/152278) while in subpopulation AFR AF = 0.0484 (2010/41520). AF 95% confidence interval is 0.0466. There are 56 homozygotes in GnomAd4. There are 997 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2142 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ACVR1C	NM_145259.3 link	c.795A>G	p.Gln265Gln	synonymous_variant	Exon 5 of 9	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2 link	c.645A>G	p.Gln215Gln	synonymous_variant	Exon 5 of 9		NP_001104501.1
ACVR1C	NM_001111032.2 link	c.555A>G	p.Gln185Gln	synonymous_variant	Exon 4 of 8		NP_001104502.1
ACVR1C	NM_001111033.2 link	c.324A>G	p.Gln108Gln	synonymous_variant	Exon 3 of 7		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ACVR1C	ENST00000243349.13 link	c.795A>G	p.Gln265Gln	synonymous_variant	Exon 5 of 9	1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7 link	c.645A>G	p.Gln215Gln	synonymous_variant	Exon 5 of 9	1		ENSP00000387168.3
ACVR1C	ENST00000335450.7 link	c.555A>G	p.Gln185Gln	synonymous_variant	Exon 4 of 8	1		ENSP00000335178.7
ACVR1C	ENST00000348328.9 link	c.324A>G	p.Gln108Gln	synonymous_variant	Exon 3 of 7	1		ENSP00000335139.6

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2143

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00433

AC:

1077

AN:

248730

AF XY:

0.00313

show subpopulations

Gnomad AFR exome

AF:

0.0518

Gnomad AMR exome

AF:

0.00509

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000310

Gnomad OTH exome

AF:

0.00460

GnomAD4 exome

AF:

0.00154

AC:

2253

AN:

1459400

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

994

AN XY:

725956

show subpopulations

African (AFR)

AF:

0.0458

AC:

1529

AN:

33358

American (AMR)

AF:

0.00537

AC:

238

AN:

44298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26046

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000584

AC:

AN:

85546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000244

AC:

271

AN:

1111058

Other (OTH)

AF:

0.00320

AC:

193

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

192

288

384

480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0141

AC:

2142

AN:

152278

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

997

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0484

AC:

2010

AN:

41520

American (AMR)

AF:

0.00614

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68030

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

103

206

308

411

514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00797

Hom.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ACVR1C-related disorder

Benign:1

Aug 13, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.54

CADD

Benign

4.1

(source)

DANN

Benign

0.57

PhyloP100

0.22

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over