2-157542998-T-A

Position:

• chr2-157542998-T-A

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.944-136A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 817,244 control chromosomes in the GnomAD database, including 257,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (40370 hom., cov: 31)
  • Exomes 𝑓: 0.80 (216737 hom.)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.294

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=-0.71).
• BP6: Variant 2-157542998-T-A is Benign according to our data. Variant chr2-157542998-T-A is described in ClinVar as [Benign]. Clinvar id is 1260053.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.944-136A>T		intron_variant		ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.794-136A>T		intron_variant			NP_001104501.1
ACVR1C	NM_001111032.2	c.704-136A>T		intron_variant			NP_001104502.1
ACVR1C	NM_001111033.2	c.473-136A>T		intron_variant			NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.944-136A>T		intron_variant		1	NM_145259.3	ENSP00000243349	P1
ACVR1C	ENST00000335450.7	c.704-136A>T		intron_variant		1		ENSP00000335178
ACVR1C	ENST00000348328.9	c.473-136A>T		intron_variant		1		ENSP00000335139
ACVR1C	ENST00000409680.7	c.794-136A>T		intron_variant		1		ENSP00000387168

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108449 AN: 151468 Hom.: 40365 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.803 AC: 534602 AN: 665658 Hom.: 216737 AF XY: 0.801 AC XY: 275619 AN XY: 344016

Gnomad4 AFR exome AF: 0.482

Gnomad4 AMR exome AF: 0.776

Gnomad4 ASJ exome AF: 0.774

Gnomad4 EAS exome AF: 0.934

Gnomad4 SAS exome AF: 0.747

Gnomad4 FIN exome AF: 0.819

Gnomad4 NFE exome AF: 0.813

Gnomad4 OTH exome AF: 0.791

GnomAD4 genome AF: 0.716 AC: 108475 AN: 151586 Hom.: 40370 Cov.: 31 AF XY: 0.719 AC XY: 53276 AN XY: 74060

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.746

Alfa AF: 0.748 Hom.: 5422

Bravo AF: 0.705

Asia WGS AF: 0.834 AC: 2900 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	-0.71
CADD	Benign	10
DANN	Benign	0.85

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: rs4254465; hg19: chr2-158399510; COSMIC: COSV54650083;