chr2-157543002-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
• Publications: 2 publications found

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145259.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1C	NM_145259.3	MANE Select	c.944-140C>A		intron	N/A	NP_660302.2	Q8NER5-1
	ACVR1C	NM_001111031.2		c.794-140C>A		intron	N/A	NP_001104501.1	Q8NER5-4
	ACVR1C	NM_001111032.2		c.704-140C>A		intron	N/A	NP_001104502.1	Q8NER5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1C	ENST00000243349.13	TSL:1 MANE Select	c.944-140C>A		intron	N/A	ENSP00000243349.7	Q8NER5-1
	ACVR1C	ENST00000409680.7	TSL:1	c.794-140C>A		intron	N/A	ENSP00000387168.3	Q8NER5-4
	ACVR1C	ENST00000335450.7	TSL:1	c.704-140C>A		intron	N/A	ENSP00000335178.7	Q8NER5-3

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

African (AFR) AF: 0.484 AC: 7411 AN: 15310

American (AMR) AF: 0.776 AC: 14894 AN: 19190

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 11406 AN: 14744

East Asian (EAS) AF: 0.934 AC: 29936 AN: 32046

South Asian (SAS) AF: 0.747 AC: 37172 AN: 49784

European-Finnish (FIN) AF: 0.819 AC: 26368 AN: 32200

Middle Eastern (MID) AF: 0.786 AC: 1810 AN: 2302

European-Non Finnish (NFE) AF: 0.812 AC: 351398 AN: 432842

Other (OTH) 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

African (AFR) AF: 0.491 AC: 20247 AN: 41260

American (AMR) AF: 0.762 AC: 11613 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2647 AN: 3462

East Asian (EAS) AF: 0.921 AC: 4720 AN: 5126

South Asian (SAS) AF: 0.758 AC: 3647 AN: 4812

European-Finnish (FIN) AF: 0.820 AC: 8621 AN: 10518

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54531 AN: 67800

Other (OTH) AF: 0.746 AC: 1574 AN: 2110

Alfa AF: 0.768 Hom.: 9246

Bravo AF: 0.705

Asia WGS AF: 0.835 AC: 2901 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.3
DANN	Benign	0.80
PhyloP100		0.067
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

Other links and lift over

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