rs13010956

chr2-157556030-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145259.3(ACVR1C):c.544+63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,522,714 control chromosomes in the GnomAD database, including 141,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11831 hom., cov: 31)
  • Exomes 𝑓: 0.43 (129970 hom.)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.222

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-157556030-T-C is Benign according to our data. Variant chr2-157556030-T-C is described in ClinVar as [Benign]. Clinvar id is 1225542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR1C	NM_145259.3	c.544+63A>G		intron_variant		ENST00000243349.13
ACVR1C	NM_001111031.2	c.394+63A>G		intron_variant
ACVR1C	NM_001111032.2	c.305-5638A>G		intron_variant
ACVR1C	NM_001111033.2	c.305-11418A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR1C	ENST00000243349.13	c.544+63A>G		intron_variant		1	NM_145259.3	P1
ACVR1C	ENST00000335450.7	c.305-5638A>G		intron_variant		1
ACVR1C	ENST00000348328.9	c.305-11418A>G		intron_variant		1
ACVR1C	ENST00000409680.7	c.394+63A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58815 AN: 151848 Hom.: 11817 Cov.: 31

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.430 AC: 589931 AN: 1370748 Hom.: 129970 AF XY: 0.427 AC XY: 288854 AN XY: 676872

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.387 AC: 58854 AN: 151966 Hom.: 11831 Cov.: 31 AF XY: 0.380 AC XY: 28207 AN XY: 74252

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.400

Alfa AF: 0.433 Hom.: 2959

Bravo AF: 0.391

Asia WGS AF: 0.270 AC: 946 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.28
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs13010956; hg19: chr2-158412542;