12-51954475-A-G

Position:

• chr12-51954475-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000257963.9(ACVR1B):​c.91+2641A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,120 control chromosomes in the GnomAD database, including 23,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (23081 hom., cov: 33)
• Consequence: ACVR1B ENST00000257963.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37

Genes affected

ACVR1B (HGNC:172): (activin A receptor type 1B) This gene encodes an activin A type IB receptor. Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I and two type II receptors. This protein is a type I receptor which is essential for signaling. Mutations in this gene are associated with pituitary tumors. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-51954475-A-G is Benign according to our data. Variant chr12-51954475-A-G is described in ClinVar as [Benign]. Clinvar id is 1287358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.91+2641A>G		intron_variant		ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9	c.91+2641A>G		intron_variant		1	NM_004302.5	ENSP00000257963	P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78722 AN: 152002 Hom.: 23073 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.518 AC: 78733 AN: 152120 Hom.: 23081 Cov.: 33 AF XY: 0.519 AC XY: 38592 AN XY: 74362

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.521

Alfa AF: 0.603 Hom.: 28839

Bravo AF: 0.477

Asia WGS AF: 0.618 AC: 2149 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

Oct 16, 2019

This variant is associated with the following publications: (PMID: 30335480) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.63

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: rs7962469; hg19: chr12-52348259;