2-157542998-T-A

Variant names:

• chr2-157542998-T-A
• rs4254465
• NM_145259.3:c.944-136A>T

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.944-136A>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
• Publications: 1 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=-0.71).
• BP6: Variant 2-157542998-T-A is Benign according to our data. Variant chr2-157542998-T-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.944-136A>T		intron	N/A	NP_660302.2	Q8NER5-1
	ACVR1C	NM_001111031.2		c.794-136A>T		intron	N/A	NP_001104501.1	Q8NER5-4
	ACVR1C	NM_001111032.2		c.704-136A>T		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.944-136A>T		intron	N/A	ENSP00000243349.7	Q8NER5-1
	ACVR1C	ENST00000409680.7	TSL:1	c.794-136A>T		intron	N/A	ENSP00000387168.3	Q8NER5-4
	ACVR1C	ENST00000335450.7	TSL:1	c.704-136A>T		intron	N/A	ENSP00000335178.7	Q8NER5-3

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

African (AFR) AF: 0.482 AC: 7726 AN: 16020

American (AMR) AF: 0.776 AC: 15428 AN: 19880

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 11652 AN: 15046

East Asian (EAS) AF: 0.934 AC: 30477 AN: 32634

South Asian (SAS) AF: 0.747 AC: 38099 AN: 51014

European-Finnish (FIN) AF: 0.819 AC: 26860 AN: 32790

Middle Eastern (MID) AF: 0.788 AC: 1844 AN: 2340

European-Non Finnish (NFE) AF: 0.813 AC: 376414 AN: 462924

Other (OTH) AF: 0.791 AC: 26102 AN: 33010

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

African (AFR) AF: 0.490 AC: 20244 AN: 41306

American (AMR) AF: 0.762 AC: 11615 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2646 AN: 3464

East Asian (EAS) AF: 0.921 AC: 4722 AN: 5128

South Asian (SAS) AF: 0.758 AC: 3645 AN: 4810

European-Finnish (FIN) AF: 0.819 AC: 8620 AN: 10526

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

European-Non Finnish (NFE) AF: 0.804 AC: 54527 AN: 67800

Other (OTH) AF: 0.746 AC: 1572 AN: 2108

Alfa AF: 0.748 Hom.: 5422

Bravo AF: 0.705

Asia WGS AF: 0.834 AC: 2900 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	-0.71
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		0.29
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: rs4254465; hg19: chr2-158399510; COSMIC: COSV54650083;