2-157544294-C-A

Position:

• chr2-157544294-C-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.943+151G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 617,834 control chromosomes in the GnomAD database, including 196,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (41385 hom., cov: 24)
  • Exomes 𝑓: 0.81 (155135 hom.)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29

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=-0.91).
• BP6: Variant 2-157544294-C-A is Benign according to our data. Variant chr2-157544294-C-A is described in ClinVar as [Benign]. Clinvar id is 1267871.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.943+151G>T		intron_variant		ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.793+151G>T		intron_variant			NP_001104501.1
ACVR1C	NM_001111032.2	c.703+151G>T		intron_variant			NP_001104502.1
ACVR1C	NM_001111033.2	c.472+151G>T		intron_variant			NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.943+151G>T		intron_variant		1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.793+151G>T		intron_variant		1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.703+151G>T		intron_variant		1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.472+151G>T		intron_variant		1		ENSP00000335139.6

Frequencies

GnomAD3 genomes AF: 0.731 AC: 109616 AN: 149916 Hom.: 41381 Cov.: 24

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.811 AC: 379254 AN: 467806 Hom.: 155135 AF XY: 0.810 AC XY: 191060 AN XY: 235834

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.777

Gnomad4 EAS exome AF: 0.939

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.827

Gnomad4 NFE exome AF: 0.817

Gnomad4 OTH exome AF: 0.794

GnomAD4 genome AF: 0.731 AC: 109640 AN: 150028 Hom.: 41385 Cov.: 24 AF XY: 0.734 AC XY: 53697 AN XY: 73198

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.754

Alfa AF: 0.763 Hom.: 5634

Bravo AF: 0.718

Asia WGS AF: 0.840 AC: 2921 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	-0.91
CADD	Benign	0.47
DANN	Benign	0.53

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: rs10432555; hg19: chr2-158400806;