rs10783486

Variant names:

• chr12-51969002-G-A
• rs10783486
• NM_004302.5:c.92-6263G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004302.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	NM_004302.5	MANE Select	c.92-6263G>A		intron	N/A	NP_004293.1
	ACVR1B	NM_020328.4		c.92-6263G>A		intron	N/A	NP_064733.3
	ACVR1B	NM_001412774.1		c.92-6263G>A		intron	N/A	NP_001399703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.92-6263G>A		intron	N/A	ENSP00000257963.4
	ACVR1B	ENST00000541224.5	TSL:2	c.92-6263G>A		intron	N/A	ENSP00000442656.1
	ACVR1B	ENST00000415850.6	TSL:2	c.92-6263G>A		intron	N/A	ENSP00000397550.2

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

African (AFR) AF: 0.260 AC: 10763 AN: 41428

American (AMR) AF: 0.479 AC: 7311 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3466

East Asian (EAS) AF: 0.308 AC: 1596 AN: 5178

South Asian (SAS) AF: 0.260 AC: 1255 AN: 4818

European-Finnish (FIN) AF: 0.238 AC: 2509 AN: 10564

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17505 AN: 67958

Other (OTH) AF: 0.307 AC: 650 AN: 2114

Alfa AF: 0.273 Hom.: 22490

Bravo AF: 0.306

Asia WGS AF: 0.331 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.84
PhyloP100		-1.4
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: rs10783486; hg19: chr12-52362786;