rs373237304

Variant names:

• chr12-51951754-C-A
• NM_004302.5:c.11C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-51951754-C-A
• chr12-51951754-C-G
• chr12-51951754-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_004302.5(ACVR1B):​c.11C>A​(p.Ser4*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000888 in 1,126,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 8.9e-7 (0 hom.)
• Consequence: ACVR1B NM_004302.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.993 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.11C>A	p.Ser4*	stop_gained	Exon 1 of 9	ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9	c.11C>A	p.Ser4*	stop_gained	Exon 1 of 9	1	NM_004302.5	ENSP00000257963.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.88e-7 AC: 1 AN: 1126692 Hom.: 0 Cov.: 31 AF XY: 0.00000186 AC XY: 1 AN XY: 537160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	39
DANN	Uncertain	0.99
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.62	D
Vest4		0.47
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-52345538;