12-51995500-C-T

Variant names:

• chr12-51995500-C-T
• rs2714
• NM_004302.5:c.*1390C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004302.5(ACVR1B):​c.*1390C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACVR1B NM_004302.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 6 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

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.*1390C>T		3_prime_UTR	Exon 9 of 9	NP_004293.1	P36896-1
	ACVR1B	NM_020328.4		c.*1390C>T		3_prime_UTR	Exon 10 of 10	NP_064733.3
	ACVR1B	NM_001412774.1		c.*1390C>T		3_prime_UTR	Exon 10 of 10	NP_001399703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.*1390C>T		3_prime_UTR	Exon 9 of 9	ENSP00000257963.4	P36896-1
	ACVR1B	ENST00000900350.1		c.*1390C>T		3_prime_UTR	Exon 10 of 10	ENSP00000570409.1
	ACVR1B	ENST00000900349.1		c.*1390C>T		3_prime_UTR	Exon 9 of 9	ENSP00000570408.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 436 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		1.8

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: rs2714; hg19: chr12-52389284;