2-157538301-T-C

Position:

• chr2-157538301-T-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.1356+272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,206 control chromosomes in the GnomAD database, including 60,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60958 hom., cov: 32)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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=-0.88).
• BP6: Variant 2-157538301-T-C is Benign according to our data. Variant chr2-157538301-T-C is described in ClinVar as [Benign]. Clinvar id is 1222596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.1356+272A>G		intron_variant		ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.1206+272A>G		intron_variant			NP_001104501.1
ACVR1C	NM_001111032.2	c.1116+272A>G		intron_variant			NP_001104502.1
ACVR1C	NM_001111033.2	c.885+272A>G		intron_variant			NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.1356+272A>G		intron_variant		1	NM_145259.3	ENSP00000243349	P1
ACVR1C	ENST00000335450.7	c.1116+272A>G		intron_variant		1		ENSP00000335178
ACVR1C	ENST00000348328.9	c.885+272A>G		intron_variant		1		ENSP00000335139
ACVR1C	ENST00000409680.7	c.1206+272A>G		intron_variant		1		ENSP00000387168

Frequencies

GnomAD3 genomes AF: 0.894 AC: 136020 AN: 152088 Hom.: 60919 Cov.: 32

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.894 AC: 136116 AN: 152206 Hom.: 60958 Cov.: 32 AF XY: 0.894 AC XY: 66511 AN XY: 74406

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.911

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.890

Alfa AF: 0.889 Hom.: 12914

Bravo AF: 0.899

Asia WGS AF: 0.889 AC: 3092 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6437105; hg19: chr2-158394813;