12-51986902-G-C

Variant names:

• chr12-51986902-G-C
• rs2641516
• NM_004302.5:c.1221G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004302.5(ACVR1B):​c.1221G>C​(p.Gly407Gly) variant causes a synonymous 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: 33)
• Consequence: ACVR1B NM_004302.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 1 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.004 with no splicing effect.

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.1221G>C	p.Gly407Gly	synonymous	Exon 7 of 9	NP_004293.1
	ACVR1B	NM_020328.4		c.1344G>C	p.Gly448Gly	synonymous	Exon 8 of 10	NP_064733.3
	ACVR1B	NM_001412774.1		c.1341G>C	p.Gly447Gly	synonymous	Exon 8 of 10	NP_001399703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.1221G>C	p.Gly407Gly	synonymous	Exon 7 of 9	ENSP00000257963.4
	ACVR1B	ENST00000541224.5	TSL:2	c.1344G>C	p.Gly448Gly	synonymous	Exon 8 of 10	ENSP00000442656.1
	ACVR1B	ENST00000415850.6	TSL:2	c.1221G>C	p.Gly407Gly	synonymous	Exon 7 of 7	ENSP00000397550.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.3
DANN	Benign	0.76
PhyloP100		0.0040

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: rs2641516; hg19: chr12-52380686;