rs10783486

Positions:

• chr12-51969002-G-A

Variant summary

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

The NM_004302.5(ACVR1B):​c.92-6263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,000 control chromosomes in the GnomAD database, including 6,457 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 0.28 (6457 hom., cov: 32)
• Consequence: ACVR1B NM_004302.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR1B	NM_004302.5	c.92-6263G>A		intron_variant		ENST00000257963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR1B	ENST00000257963.9	c.92-6263G>A		intron_variant		1	NM_004302.5	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42636 AN: 151882 Hom.: 6437 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.281 AC: 42687 AN: 152000 Hom.: 6457 Cov.: 32 AF XY: 0.284 AC XY: 21106 AN XY: 74288

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.307

Alfa AF: 0.274 Hom.: 11296

Bravo AF: 0.306

Asia WGS AF: 0.331 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.84

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: rs10783486; hg19: chr12-52362786;