Variant rs4556933 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_145259.3(ACVR1C):c.114C>T(p.Phe38Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,612,616 control chromosomes in the GnomAD database, including 131,012 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 17413 hom., cov: 31)

Exomes 𝑓: 0.39 ( 113599 hom. )

Consequence

ACVR1C
NM_145259.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP7

Synonymous conserved (PhyloP=1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1C	NM_145259.3 link	c.114C>T	p.Phe38Phe	synonymous_variant	2/9	ENST00000243349.13	NP_660302.2	Q8NER5-1
ACVR1C	NM_001111032.2 link	c.114C>T	p.Phe38Phe	synonymous_variant	2/8		NP_001104502.1	Q8NER5-3
ACVR1C	NM_001111033.2 link	c.114C>T	p.Phe38Phe	synonymous_variant	2/7		NP_001104503.1	Q8NER5-2
ACVR1C	NM_001111031.2 link	c.-37C>T		5_prime_UTR_variant	2/9		NP_001104501.1	Q8NER5-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACVR1C	ENST00000243349.13 link	c.114C>T	p.Phe38Phe	synonymous_variant	2/9	1	NM_145259.3	ENSP00000243349.7	Q8NER5-1
ACVR1C	ENST00000335450.7 link	c.114C>T	p.Phe38Phe	synonymous_variant	2/8	1		ENSP00000335178.7	Q8NER5-3
ACVR1C	ENST00000348328.9 link	c.114C>T	p.Phe38Phe	synonymous_variant	2/7	1		ENSP00000335139.6	Q8NER5-2
ACVR1C	ENST00000409680.7 link	c.-37C>T		5_prime_UTR_variant	2/9	1		ENSP00000387168.3	Q8NER5-4

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69646

AN:

151642

Hom.:

17380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.659

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.456

GnomAD3 exomes

AF:

0.386

AC:

97068

AN:

251276

Hom.:

19913

AF XY:

0.375

AC XY:

50994

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.668

Gnomad AMR exome

AF:

0.420

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.316

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.395

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.389

AC:

568494

AN:

1460858

Hom.:

113599

Cov.:

AF XY:

0.385

AC XY:

279504

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.665

Gnomad4 AMR exome

AF:

0.423

Gnomad4 ASJ exome

AF:

0.410

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.273

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.460

AC:

69733

AN:

151758

Hom.:

17413

Cov.:

AF XY:

0.450

AC XY:

33350

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.660

Gnomad4 AMR

AF:

0.440

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.286

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.398

Gnomad4 OTH

AF:

0.455

Alfa

AF:

0.408

Hom.:

31813

Bravo

AF:

0.483

Asia WGS

AF:

0.334

AC:

1167

AN:

3478

EpiCase

AF:

0.401

EpiControl

AF:

0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.7

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over