Genetic Variant ACVR1B:c.*997A>G (chr12-51995107-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004302.5(ACVR1B):c.*997A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,986 control chromosomes in the GnomAD database, including 9,546 homozygotes. 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: 𝑓 0.34 ( 9508 hom., cov: 31)

Exomes 𝑓: 0.27 ( 38 hom. )

Consequence

ACVR1B
NM_004302.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Publications

29 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1B	NM_004302.5 link	c.*997A>G		3_prime_UTR_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 link	c.*997A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_004302.5	ENSP00000257963.4
ACVR1B	ENST00000542485.1 link	c.*997A>G		downstream_gene_variant		2		ENSP00000442885.1

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51243

AN:

151884

Hom.:

9479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.344

GnomAD4 exome

AF:

0.274

AC:

270

AN:

984

Hom.:

Cov.:

AF XY:

0.285

AC XY:

151

AN XY:

530

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.393

AC:

AN:

140

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

109

AN:

436

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.252

AC:

AN:

286

Other (OTH)

AF:

0.269

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.338

AC:

51314

AN:

152002

Hom.:

9508

Cov.:

AF XY:

0.340

AC XY:

25227

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.441

AC:

18270

AN:

41424

American (AMR)

AF:

0.507

AC:

7741

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

870

AN:

3472

East Asian (EAS)

AF:

0.324

AC:

1669

AN:

5158

South Asian (SAS)

AF:

0.268

AC:

1292

AN:

4818

European-Finnish (FIN)

AF:

0.243

AC:

2568

AN:

10564

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17863

AN:

67968

Other (OTH)

AF:

0.339

AC:

716

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1646

3291

4937

6582

8228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.296

Hom.:

19255

Bravo

AF:

0.368

Asia WGS

AF:

0.349

AC:

1212

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.050

(source)

DANN

Benign

0.65

PhyloP100

-2.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.2

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over