2-157544202-A-AT

Position:

• chr2-157544202-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_145259.3(ACVR1C):​c.943+242_943+243insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 116,872 control chromosomes in the GnomAD database, including 86 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.022 (86 hom., cov: 25)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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-A-AT is Benign according to our data. Variant chr2-157544202-A-AT is described in ClinVar as [Benign]. Clinvar id is 1230041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.943+242_943+243insA		intron_variant		ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.793+242_793+243insA		intron_variant			NP_001104501.1
ACVR1C	NM_001111032.2	c.703+242_703+243insA		intron_variant			NP_001104502.1
ACVR1C	NM_001111033.2	c.472+242_472+243insA		intron_variant			NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.943+242_943+243insA		intron_variant		1	NM_145259.3	ENSP00000243349	P1
ACVR1C	ENST00000335450.7	c.703+242_703+243insA		intron_variant		1		ENSP00000335178
ACVR1C	ENST00000348328.9	c.472+242_472+243insA		intron_variant		1		ENSP00000335139
ACVR1C	ENST00000409680.7	c.793+242_793+243insA		intron_variant		1		ENSP00000387168

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 2548 AN: 116902 Hom.: 86 Cov.: 25

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.00636

Gnomad AMR AF: 0.00909

Gnomad ASJ AF: 0.00413

Gnomad EAS AF: 0.00937

Gnomad SAS AF: 0.00555

Gnomad FIN AF: 0.00662

Gnomad MID AF: 0.00901

Gnomad NFE AF: 0.00686

Gnomad OTH AF: 0.0217

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

GnomAD4 genome AF: 0.0218 AC: 2549 AN: 116872 Hom.: 86 Cov.: 25 AF XY: 0.0213 AC XY: 1191 AN XY: 55932

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.00908

Gnomad4 ASJ AF: 0.00413

Gnomad4 EAS AF: 0.00940

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00662

Gnomad4 NFE AF: 0.00686

Gnomad4 OTH AF: 0.0216

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;