Genetic Variant NM_004302.5: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.

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.*997A>G	3_prime_UTR	Exon 9 of 9	NP_004293.1
ACVR1B	NR_182041.1		n.2435A>G	non_coding_transcript_exon	Exon 8 of 8
ACVR1B	NR_182042.1		n.2558A>G	non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.*997A>G		3_prime_UTR	Exon 9 of 9	ENSP00000257963.4
	ACVR1B	ENST00000542485.1	TSL:2	c.*997A>G		downstream_gene	N/A	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over