2-157543065-G-A

Position:

• chr2-157543065-G-A

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.944-203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 152,284 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (185 hom., cov: 32)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.165

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=-0.85).
• BP6: Variant 2-157543065-G-A is Benign according to our data. Variant chr2-157543065-G-A is described in ClinVar as [Benign]. Clinvar id is 1231031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.944-203C>T		intron_variant		ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.794-203C>T		intron_variant			NP_001104501.1
ACVR1C	NM_001111032.2	c.704-203C>T		intron_variant			NP_001104502.1
ACVR1C	NM_001111033.2	c.473-203C>T		intron_variant			NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.944-203C>T		intron_variant		1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.794-203C>T		intron_variant		1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.704-203C>T		intron_variant		1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.473-203C>T		intron_variant		1		ENSP00000335139.6

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6544 AN: 152166 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0430 AC: 6546 AN: 152284 Hom.: 185 Cov.: 32 AF XY: 0.0418 AC XY: 3109 AN XY: 74462

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.0287

Gnomad4 NFE AF: 0.0634

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0585 Hom.: 56

Bravo AF: 0.0427

Asia WGS AF: 0.0170 AC: 59 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	-0.85
CADD	Benign	2.0
DANN	Benign	0.44

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: rs45501693; hg19: chr2-158399577;