chr12-51954475-A-G

Variant names:

• chr12-51954475-A-G
• rs7962469
• NM_004302.5:c.91+2641A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004302.5(ACVR1B):​c.91+2641A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,120 control chromosomes in the GnomAD database, including 23,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (23081 hom., cov: 33)
• Consequence: ACVR1B NM_004302.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-51954475-A-G is Benign according to our data. Variant chr12-51954475-A-G is described in ClinVar as Benign. ClinVar VariationId is 1287358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	NM_004302.5	MANE Select	c.91+2641A>G		intron	N/A	NP_004293.1	P36896-1
	ACVR1B	NM_020328.4		c.91+2641A>G		intron	N/A	NP_064733.3
	ACVR1B	NM_001412774.1		c.91+2641A>G		intron	N/A	NP_001399703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.91+2641A>G		intron	N/A	ENSP00000257963.4	P36896-1
	ACVR1B	ENST00000541224.5	TSL:2	c.91+2641A>G		intron	N/A	ENSP00000442656.1	P36896-4
	ACVR1B	ENST00000900350.1		c.91+2641A>G		intron	N/A	ENSP00000570409.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78722 AN: 152002 Hom.: 23073 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.518 AC: 78733 AN: 152120 Hom.: 23081 Cov.: 33 AF XY: 0.519 AC XY: 38592 AN XY: 74362

African (AFR) AF: 0.247 AC: 10250 AN: 41492

American (AMR) AF: 0.402 AC: 6142 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2329 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3591 AN: 5186

South Asian (SAS) AF: 0.678 AC: 3270 AN: 4824

European-Finnish (FIN) AF: 0.675 AC: 7124 AN: 10556

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44115 AN: 67982

Other (OTH) AF: 0.521 AC: 1101 AN: 2112

Alfa AF: 0.587 Hom.: 35371

Bravo AF: 0.477

Asia WGS AF: 0.618 AC: 2149 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.63
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: rs7962469; hg19: chr12-52348259;