rs11612312

Positions:

• chr12-51955304-T-C

Variant summary

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

The NM_004302.5(ACVR1B):​c.91+3470T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,210 control chromosomes in the GnomAD database, including 3,666 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 0.19 (3666 hom., cov: 33)
• Consequence: ACVR1B NM_004302.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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=-0.61).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.91+3470T>C		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+3470T>C		intron_variant		1	NM_004302.5	ENSP00000257963	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28336 AN: 152092 Hom.: 3653 Cov.: 33

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.186 AC: 28347 AN: 152210 Hom.: 3666 Cov.: 33 AF XY: 0.192 AC XY: 14289 AN XY: 74424

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.229

Alfa AF: 0.210 Hom.: 7415

Bravo AF: 0.205

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.70

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: rs11612312; hg19: chr12-52349088;