rs13010956

Variant names:

• chr2-157556030-T-C
• rs13010956
• NM_145259.3:c.544+63A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145259.3(ACVR1C):​c.544+63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,522,714 control chromosomes in the GnomAD database, including 141,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11831 hom., cov: 31)
  • Exomes 𝑓: 0.43 (129970 hom.)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.222
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-157556030-T-C is Benign according to our data. Variant chr2-157556030-T-C is described in ClinVar as Benign. ClinVar VariationId is 1225542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1C	NM_145259.3	MANE Select	c.544+63A>G		intron	N/A	NP_660302.2
	ACVR1C	NM_001111031.2		c.394+63A>G		intron	N/A	NP_001104501.1
	ACVR1C	NM_001111032.2		c.305-5638A>G		intron	N/A	NP_001104502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1C	ENST00000243349.13	TSL:1 MANE Select	c.544+63A>G		intron	N/A	ENSP00000243349.7
	ACVR1C	ENST00000409680.7	TSL:1	c.394+63A>G		intron	N/A	ENSP00000387168.3
	ACVR1C	ENST00000335450.7	TSL:1	c.305-5638A>G		intron	N/A	ENSP00000335178.7

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58815 AN: 151848 Hom.: 11817 Cov.: 31

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.430 AC: 589931 AN: 1370748 Hom.: 129970 AF XY: 0.427 AC XY: 288854 AN XY: 676872

African (AFR) AF: 0.292 AC: 8583 AN: 29344

American (AMR) AF: 0.391 AC: 12447 AN: 31800

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 10061 AN: 23104

East Asian (EAS) AF: 0.237 AC: 8487 AN: 35800

South Asian (SAS) AF: 0.278 AC: 20123 AN: 72444

European-Finnish (FIN) AF: 0.353 AC: 16956 AN: 47976

Middle Eastern (MID) AF: 0.402 AC: 2153 AN: 5354

European-Non Finnish (NFE) AF: 0.456 AC: 487485 AN: 1068254

Other (OTH) AF: 0.417 AC: 23636 AN: 56672

GnomAD4 genome AF: 0.387 AC: 58854 AN: 151966 Hom.: 11831 Cov.: 31 AF XY: 0.380 AC XY: 28207 AN XY: 74252

African (AFR) AF: 0.309 AC: 12787 AN: 41412

American (AMR) AF: 0.411 AC: 6279 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3466

East Asian (EAS) AF: 0.250 AC: 1291 AN: 5172

South Asian (SAS) AF: 0.284 AC: 1365 AN: 4808

European-Finnish (FIN) AF: 0.336 AC: 3546 AN: 10550

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30882 AN: 67970

Other (OTH) AF: 0.400 AC: 844 AN: 2112

Alfa AF: 0.433 Hom.: 2959

Bravo AF: 0.391

Asia WGS AF: 0.270 AC: 946 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.65
PhyloP100		-0.22
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: rs13010956; hg19: chr2-158412542;