rs12809597

Variant names:

• chr12-51962539-T-G
• rs12809597
• NM_004302.5:c.91+10705T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004302.5(ACVR1B):​c.91+10705T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,088 control chromosomes in the GnomAD database, including 5,520 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 0.26 (5520 hom., cov: 32)
• Consequence: ACVR1B NM_004302.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.91+10705T>G		intron_variant	Intron 1 of 8	ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9	c.91+10705T>G		intron_variant	Intron 1 of 8	1	NM_004302.5	ENSP00000257963.4

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39244 AN: 151970 Hom.: 5522 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.258 AC: 39246 AN: 152088 Hom.: 5520 Cov.: 32 AF XY: 0.255 AC XY: 18962 AN XY: 74360

African (AFR) AF: 0.198 AC: 8210 AN: 41460

American (AMR) AF: 0.210 AC: 3209 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1036 AN: 3470

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5186

South Asian (SAS) AF: 0.201 AC: 972 AN: 4828

European-Finnish (FIN) AF: 0.305 AC: 3221 AN: 10572

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21661 AN: 67972

Other (OTH) AF: 0.262 AC: 552 AN: 2110

Alfa AF: 0.296 Hom.: 15141

Bravo AF: 0.245

Asia WGS AF: 0.0990 AC: 346 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		-0.049
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: rs12809597; hg19: chr12-52356323;