rs2641530

Positions:

• chr12-51991027-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004302.5(ACVR1B):​c.1262-836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,984 control chromosomes in the GnomAD database, including 28,559 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (28559 hom., cov: 32)
• Consequence: ACVR1B NM_004302.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.1262-836C>T		intron_variant		ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9	c.1262-836C>T		intron_variant		1	NM_004302.5	ENSP00000257963	P1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88938 AN: 151866 Hom.: 28551 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.585 AC: 88973 AN: 151984 Hom.: 28559 Cov.: 32 AF XY: 0.588 AC XY: 43665 AN XY: 74304

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.599

Alfa AF: 0.682 Hom.: 48459

Bravo AF: 0.545

Asia WGS AF: 0.645 AC: 2245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.71

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: rs2641530; hg19: chr12-52384811;