2-157534254-G-A

Variant names:

• chr2-157534254-G-A
• rs4261678
• NM_145259.3:c.1357-211C>T

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.1357-211C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 151,828 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.015 (58 hom., cov: 31)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.340

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=-1.0).
• BP6: Variant 2-157534254-G-A is Benign according to our data. Variant chr2-157534254-G-A is described in ClinVar as [Benign]. Clinvar id is 1265128.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (2240/151828) while in subpopulation AFR AF= 0.051 (2110/41374). AF 95% confidence interval is 0.0492. There are 58 homozygotes in gnomad4. There are 1066 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2240 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.1357-211C>T		intron_variant	Intron 8 of 8	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.1207-211C>T		intron_variant	Intron 8 of 8		NP_001104501.1
ACVR1C	NM_001111032.2	c.1117-211C>T		intron_variant	Intron 7 of 7		NP_001104502.1
ACVR1C	NM_001111033.2	c.886-211C>T		intron_variant	Intron 6 of 6		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.1357-211C>T		intron_variant	Intron 8 of 8	1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.1207-211C>T		intron_variant	Intron 8 of 8	1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.1117-211C>T		intron_variant	Intron 7 of 7	1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.886-211C>T		intron_variant	Intron 6 of 6	1		ENSP00000335139.6

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2232 AN: 151710 Hom.: 58 Cov.: 31

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00585

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0149

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

GnomAD4 genome AF: 0.0148 AC: 2240 AN: 151828 Hom.: 58 Cov.: 31 AF XY: 0.0144 AC XY: 1066 AN XY: 74198

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.00584

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00847 Hom.: 3

Bravo AF: 0.0169

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

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.82
DANN	Benign	0.31

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: rs4261678; hg19: chr2-158390766;