rs2641530

Variant names:

• chr12-51991027-C-T
• rs2641530
• NM_004302.5:c.1262-836C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACVR1B Gene-Disease associations (from GenCC):

• malignant pancreatic neoplasm

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.1262-836C>T		intron_variant	Intron 7 of 8	ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9	c.1262-836C>T		intron_variant	Intron 7 of 8	1	NM_004302.5	ENSP00000257963.4

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

African (AFR) AF: 0.326 AC: 13499 AN: 41400

American (AMR) AF: 0.462 AC: 7053 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2656 AN: 3468

East Asian (EAS) AF: 0.691 AC: 3569 AN: 5168

South Asian (SAS) AF: 0.731 AC: 3518 AN: 4812

European-Finnish (FIN) AF: 0.750 AC: 7926 AN: 10570

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48624 AN: 67982

Other (OTH) AF: 0.599 AC: 1263 AN: 2110

Alfa AF: 0.665 Hom.: 64523

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
PhyloP100		0.040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2641530; hg19: chr12-52384811;