2-157543002-G-T

Variant names:

• chr2-157543002-G-T
• rs4461222
• NM_145259.3:c.944-140C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145259.3(ACVR1C):​c.944-140C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 781,776 control chromosomes in the GnomAD database, including 244,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (40374 hom., cov: 31)
  • Exomes 𝑓: 0.80 (204427 hom.)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0670

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 2-157543002-G-T is Benign according to our data. Variant chr2-157543002-G-T is described in ClinVar as [Benign]. Clinvar id is 1252696.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 rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.944-140C>A		intron_variant	Intron 5 of 8	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.794-140C>A		intron_variant	Intron 5 of 8		NP_001104501.1
ACVR1C	NM_001111032.2	c.704-140C>A		intron_variant	Intron 4 of 7		NP_001104502.1
ACVR1C	NM_001111033.2	c.473-140C>A		intron_variant	Intron 3 of 6		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.944-140C>A		intron_variant	Intron 5 of 8	1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.794-140C>A		intron_variant	Intron 5 of 8	1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.704-140C>A		intron_variant	Intron 4 of 7	1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.473-140C>A		intron_variant	Intron 3 of 6	1		ENSP00000335139.6

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108458 AN: 151406 Hom.: 40369 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.802 AC: 505555 AN: 630252 Hom.: 204427 AF XY: 0.800 AC XY: 261517 AN XY: 326708

Gnomad4 AFR exome AF: 0.484 AC: 7411 AN: 15310

Gnomad4 AMR exome AF: 0.776 AC: 14894 AN: 19190

Gnomad4 ASJ exome AF: 0.774 AC: 11406 AN: 14744

Gnomad4 EAS exome AF: 0.934 AC: 29936 AN: 32046

Gnomad4 SAS exome AF: 0.747 AC: 37172 AN: 49784

Gnomad4 FIN exome AF: 0.819 AC: 26368 AN: 32200

Gnomad4 NFE exome AF: 0.812 AC: 351398 AN: 432842

Gnomad4 Remaining exome AF: 0.790 AC: 25160 AN: 31834

GnomAD4 genome AF: 0.716 AC: 108484 AN: 151524 Hom.: 40374 Cov.: 31 AF XY: 0.720 AC XY: 53283 AN XY: 74038

Gnomad4 AFR AF: 0.491 AC: 0.490717 AN: 0.490717

Gnomad4 AMR AF: 0.762 AC: 0.762108 AN: 0.762108

Gnomad4 ASJ AF: 0.765 AC: 0.764587 AN: 0.764587

Gnomad4 EAS AF: 0.921 AC: 0.920796 AN: 0.920796

Gnomad4 SAS AF: 0.758 AC: 0.757897 AN: 0.757897

Gnomad4 FIN AF: 0.820 AC: 0.819643 AN: 0.819643

Gnomad4 NFE AF: 0.804 AC: 0.804292 AN: 0.804292

Gnomad4 OTH AF: 0.746 AC: 0.745972 AN: 0.745972

Alfa AF: 0.768 Hom.: 9246

Bravo AF: 0.705

Asia WGS AF: 0.835 AC: 2901 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.3
DANN	Benign	0.80
Mutation Taster		=100/0	polymorphism (auto)

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: rs4461222; hg19: chr2-158399514; COSMIC: COSV54650093;