2-157544202-ATT-A

Position:

• chr2-157544202-ATT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_145259.3(ACVR1C):​c.943+241_943+242del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 116,868 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.013 (22 hom., cov: 25)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.842

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 -10 ACMG points.

• BP6: Variant 2-157544202-ATT-A is Benign according to our data. Variant chr2-157544202-ATT-A is described in ClinVar as [Benign]. Clinvar id is 1235792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (1561/116868) while in subpopulation AFR AF= 0.0476 (1456/30606). AF 95% confidence interval is 0.0455. There are 22 homozygotes in gnomad4. There are 726 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1561 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.943+241_943+242del		intron_variant		ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.793+241_793+242del		intron_variant			NP_001104501.1
ACVR1C	NM_001111032.2	c.703+241_703+242del		intron_variant			NP_001104502.1
ACVR1C	NM_001111033.2	c.472+241_472+242del		intron_variant			NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.943+241_943+242del		intron_variant		1	NM_145259.3	ENSP00000243349	P1
ACVR1C	ENST00000335450.7	c.703+241_703+242del		intron_variant		1		ENSP00000335178
ACVR1C	ENST00000348328.9	c.472+241_472+242del		intron_variant		1		ENSP00000335139
ACVR1C	ENST00000409680.7	c.793+241_793+242del		intron_variant		1		ENSP00000387168

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 1558 AN: 116898 Hom.: 21 Cov.: 25

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00565

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000264

Gnomad FIN AF: 0.000537

Gnomad MID AF: 0.00901

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0138

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

GnomAD4 genome AF: 0.0134 AC: 1561 AN: 116868 Hom.: 22 Cov.: 25 AF XY: 0.0130 AC XY: 726 AN XY: 55922

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.00565

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000266

Gnomad4 FIN AF: 0.000537

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0138

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

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: rs765521635; hg19: chr2-158400714;