12-51982700-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_020328.4(ACVR1B):c.826C>T(p.Leu276Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,531,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

ACVR1B
NM_020328.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0480

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 3.3735 (above the threshold of 3.09). Trascript score misZ: 4.4731 (above the threshold of 3.09). GenCC associations: The gene is linked to malignant pancreatic neoplasm.

BP4

Computational evidence support a benign effect (MetaRNN=0.10134536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020328.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACVR1B	NM_004302.5	MANE Select	c.812-1299C>T		intron	N/A	NP_004293.1	P36896-1
ACVR1B	NM_020328.4		c.826C>T	p.Leu276Phe	missense	Exon 5 of 10	NP_064733.3
ACVR1B	NM_001412774.1		c.823C>T	p.Leu275Phe	missense	Exon 5 of 10	NP_001399703.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.812-1299C>T		intron	N/A	ENSP00000257963.4	P36896-1
ACVR1B	ENST00000541224.5	TSL:2	c.826C>T	p.Leu276Phe	missense	Exon 5 of 10	ENSP00000442656.1	P36896-4
ACVR1B	ENST00000900350.1		c.823C>T	p.Leu275Phe	missense	Exon 5 of 10	ENSP00000570409.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000382

AC:

AN:

130822

AF XY:

0.0000420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000772

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000500

AC:

AN:

1379244

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

680408

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31402

American (AMR)

AF:

0.00

AC:

AN:

34876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25050

East Asian (EAS)

AF:

0.00

AC:

AN:

35500

South Asian (SAS)

AF:

0.00

AC:

AN:

78220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.0000594

AC:

AN:

1076952

Other (OTH)

AF:

0.0000693

AC:

AN:

57708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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

AF:

0.0000394

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.7

(source)

DANN

Benign

0.97

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.34

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.10

MetaSVM

Uncertain

-0.20

PhyloP100

0.048

PrimateAI

Benign

0.39

PROVEAN

Benign

0.070

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.25

MutPred

0.54

Gain of catalytic residue at L278 (P = 0)

MVP

0.40

MPC

1.1

ClinPred

0.036

GERP RS

0.73

gMVP

0.40

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over