rs13097628

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001106.4(ACVR2B):​c.811-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,612,976 control chromosomes in the GnomAD database, including 232,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16310 hom., cov: 31)
Exomes 𝑓: 0.54 ( 216073 hom. )

Consequence

ACVR2B
NM_001106.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.35

Publications

18 publications found
Variant links:
Genes affected
ACVR2B (HGNC:174): (activin A receptor type 2B) 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 (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. Type II receptors are considered to be constitutively active kinases. This gene encodes activin A type IIB receptor, which displays a 3- to 4-fold higher affinity for the ligand than activin A type II receptor. [provided by RefSeq, Jul 2008]
ACVR2B Gene-Disease associations (from GenCC):
  • heterotaxy, visceral, 4, autosomal
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 3-38479665-T-C is Benign according to our data. Variant chr3-38479665-T-C is described in ClinVar as Benign. ClinVar VariationId is 257470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001106.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ACVR2B
NM_001106.4
MANE Select
c.811-13T>C
intron
N/ANP_001097.2Q13705-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ACVR2B
ENST00000352511.5
TSL:1 MANE Select
c.811-13T>C
intron
N/AENSP00000340361.3Q13705-1
ACVR2B
ENST00000461232.1
TSL:1
n.4600-13T>C
intron
N/A
ACVR2B
ENST00000922132.1
c.787-13T>C
intron
N/AENSP00000592191.1

Frequencies

GnomAD3 genomes
AF:
0.430
AC:
65343
AN:
151940
Hom.:
16310
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.188
Gnomad AMI
AF:
0.465
Gnomad AMR
AF:
0.388
Gnomad ASJ
AF:
0.499
Gnomad EAS
AF:
0.269
Gnomad SAS
AF:
0.510
Gnomad FIN
AF:
0.531
Gnomad MID
AF:
0.475
Gnomad NFE
AF:
0.573
Gnomad OTH
AF:
0.453
GnomAD2 exomes
AF:
0.478
AC:
119884
AN:
250868
AF XY:
0.492
show subpopulations
Gnomad AFR exome
AF:
0.184
Gnomad AMR exome
AF:
0.334
Gnomad ASJ exome
AF:
0.506
Gnomad EAS exome
AF:
0.270
Gnomad FIN exome
AF:
0.533
Gnomad NFE exome
AF:
0.572
Gnomad OTH exome
AF:
0.501
GnomAD4 exome
AF:
0.537
AC:
783894
AN:
1460916
Hom.:
216073
Cov.:
45
AF XY:
0.538
AC XY:
390834
AN XY:
726762
show subpopulations
African (AFR)
AF:
0.173
AC:
5795
AN:
33466
American (AMR)
AF:
0.340
AC:
15183
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
0.498
AC:
13012
AN:
26124
East Asian (EAS)
AF:
0.305
AC:
12116
AN:
39678
South Asian (SAS)
AF:
0.520
AC:
44838
AN:
86146
European-Finnish (FIN)
AF:
0.541
AC:
28835
AN:
53292
Middle Eastern (MID)
AF:
0.478
AC:
2757
AN:
5768
European-Non Finnish (NFE)
AF:
0.568
AC:
630958
AN:
1111376
Other (OTH)
AF:
0.504
AC:
30400
AN:
60360
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
19594
39187
58781
78374
97968
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
17206
34412
51618
68824
86030
<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:
0.430
AC:
65352
AN:
152060
Hom.:
16310
Cov.:
31
AF XY:
0.427
AC XY:
31711
AN XY:
74304
show subpopulations
African (AFR)
AF:
0.188
AC:
7794
AN:
41508
American (AMR)
AF:
0.388
AC:
5933
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.499
AC:
1732
AN:
3470
East Asian (EAS)
AF:
0.269
AC:
1388
AN:
5160
South Asian (SAS)
AF:
0.511
AC:
2453
AN:
4804
European-Finnish (FIN)
AF:
0.531
AC:
5617
AN:
10570
Middle Eastern (MID)
AF:
0.480
AC:
141
AN:
294
European-Non Finnish (NFE)
AF:
0.573
AC:
38913
AN:
67942
Other (OTH)
AF:
0.453
AC:
957
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1710
3421
5131
6842
8552
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
606
1212
1818
2424
3030
<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:
0.498
Hom.:
6848
Bravo
AF:
0.404
Asia WGS
AF:
0.404
AC:
1403
AN:
3478

ClinVar

ClinVar submissions
Significance:Benign
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
5
Heterotaxy, visceral, 4, autosomal (5)
-
-
4
not specified (4)
-
-
2
not provided (2)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
8.0
DANN
Benign
0.70
PhyloP100
2.4
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs13097628; hg19: chr3-38521156; COSMIC: COSV107429761; API
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.