2-157542526-G-C

Position:

• chr2-157542526-G-C

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.1100+180C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 152,254 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.051 (288 hom., cov: 32)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.943

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=-0.87).
• BP6: Variant 2-157542526-G-C is Benign according to our data. Variant chr2-157542526-G-C is described in ClinVar as [Benign]. Clinvar id is 1272276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.1100+180C>G		intron_variant		ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.950+180C>G		intron_variant			NP_001104501.1
ACVR1C	NM_001111032.2	c.860+180C>G		intron_variant			NP_001104502.1
ACVR1C	NM_001111033.2	c.629+180C>G		intron_variant			NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.1100+180C>G		intron_variant		1	NM_145259.3	ENSP00000243349	P1
ACVR1C	ENST00000335450.7	c.860+180C>G		intron_variant		1		ENSP00000335178
ACVR1C	ENST00000348328.9	c.629+180C>G		intron_variant		1		ENSP00000335139
ACVR1C	ENST00000409680.7	c.950+180C>G		intron_variant		1		ENSP00000387168

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7703 AN: 152136 Hom.: 288 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0657

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.0402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0506 AC: 7700 AN: 152254 Hom.: 288 Cov.: 32 AF XY: 0.0483 AC XY: 3596 AN XY: 74428

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0669

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0657

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0311 Hom.: 27

Bravo AF: 0.0463

Asia WGS AF: 0.00808 AC: 29 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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.015
DANN	Benign	0.65

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: rs75349715; hg19: chr2-158399038;