chr2-157538407-T-C

Position:

• chr2-157538407-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145259.3(ACVR1C):​c.1356+166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 152,276 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.013 (52 hom., cov: 32)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.00

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=-0.89).
• BP6: Variant 2-157538407-T-C is Benign according to our data. Variant chr2-157538407-T-C is described in ClinVar as [Benign]. Clinvar id is 1265317.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1996/152276) while in subpopulation AFR AF= 0.0455 (1890/41538). AF 95% confidence interval is 0.0438. There are 52 homozygotes in gnomad4. There are 943 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1996 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.1356+166A>G		intron_variant		ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.1206+166A>G		intron_variant			NP_001104501.1
ACVR1C	NM_001111032.2	c.1116+166A>G		intron_variant			NP_001104502.1
ACVR1C	NM_001111033.2	c.885+166A>G		intron_variant			NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.1356+166A>G		intron_variant		1	NM_145259.3	ENSP00000243349	P1
ACVR1C	ENST00000335450.7	c.1116+166A>G		intron_variant		1		ENSP00000335178
ACVR1C	ENST00000348328.9	c.885+166A>G		intron_variant		1		ENSP00000335139
ACVR1C	ENST00000409680.7	c.1206+166A>G		intron_variant		1		ENSP00000387168

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1980 AN: 152158 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0131 AC: 1996 AN: 152276 Hom.: 52 Cov.: 32 AF XY: 0.0127 AC XY: 943 AN XY: 74460

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.00985 Hom.: 3

Bravo AF: 0.0152

Asia WGS AF: 0.00289 AC: 10 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.68

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: rs116499466; hg19: chr2-158394919;