Genetic Variant ACVR1B:c.1261+172G>T (chr12-51987114-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004302.5(ACVR1B):c.1261+172G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 715,172 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ACVR1B
NM_004302.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.519

Publications

0 publications found

Variant links:

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

ACVR1B links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.20422465).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACVR1B	NM_004302.5	MANE Select	c.1261+172G>T	intron	N/A	NP_004293.1
ACVR1B	NM_020328.4		c.1384+172G>T	intron	N/A	NP_064733.3
ACVR1B	NM_001412774.1		c.1381+172G>T	intron	N/A	NP_001399703.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.1261+172G>T		intron	N/A	ENSP00000257963.4
ACVR1B	ENST00000415850.6	TSL:2	c.1433G>T	p.Arg478Leu	missense	Exon 7 of 7	ENSP00000397550.2
ACVR1B	ENST00000541224.5	TSL:2	c.1384+172G>T		intron	N/A	ENSP00000442656.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000280

AC:

AN:

715172

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

378518

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18586

American (AMR)

AF:

0.00

AC:

AN:

35726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20976

East Asian (EAS)

AF:

0.00

AC:

AN:

33744

South Asian (SAS)

AF:

0.00

AC:

AN:

67612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4390

European-Non Finnish (NFE)

AF:

0.00000446

AC:

AN:

448300

Other (OTH)

AF:

0.00

AC:

AN:

35588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

3.8

(source)

DANN

Benign

0.76

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.26

M_CAP

Benign

0.083

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.91

PhyloP100

0.52

PROVEAN

Benign

-1.2

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.21

MutPred

0.66

Gain of catalytic residue at F480 (P = 0.0178)

MVP

0.60

ClinPred

0.15

GERP RS

0.36

Mutation Taster

=93/7

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over