chr12-51993995-T-A

Variant names:

• chr12-51993995-T-A
• NM_004302.5:c.1403T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004302.5(ACVR1B):​c.1403T>A​(p.Val468Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: ACVR1B NM_004302.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.1403T>A	p.Val468Glu	missense_variant	Exon 9 of 9	ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9	c.1403T>A	p.Val468Glu	missense_variant	Exon 9 of 9	1	NM_004302.5	ENSP00000257963.4
ACVR1B	ENST00000541224.5	c.1526T>A	p.Val509Glu	missense_variant	Exon 10 of 10	2		ENSP00000442656.1
ACVR1B	ENST00000542485.1	c.1247T>A	p.Val416Glu	missense_variant	Exon 9 of 9	2		ENSP00000442885.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	30
DANN	Benign	0.95
DEOGEN2	Benign	0.24	T;.;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.24	N;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Uncertain	0.55
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.92	T;T;T
Polyphen		0.96	D;B;.
Vest4		0.84
MutPred		0.49		Gain of catalytic residue at M473 (P = 2e-04);.;.;
MVP		0.88
MPC		2.6
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.66
gMVP		0.93

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: chr12-52387779;