dbSNP rs35364034: BTBD3:p.Ala303Ala (chr20-11923006-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014962.4(BTBD3):c.909G>A(p.Ala303Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,614,150 control chromosomes in the GnomAD database, including 4,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 369 hom., cov: 33)

Exomes 𝑓: 0.057 ( 3674 hom. )

Consequence

BTBD3
NM_014962.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.908

Publications

11 publications found

Variant links:

Genes affected

BTBD3 (HGNC:15854): (BTB domain containing 3) Enables identical protein binding activity. Predicted to be involved in cerebral cortex development and dendrite morphogenesis. Predicted to be located in nucleus. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

BTBD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 20-11923006-G-A is Benign according to our data. Variant chr20-11923006-G-A is described in ClinVar as Benign. ClinVar VariationId is 1226908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.908 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD3	NM_014962.4 link	c.909G>A	p.Ala303Ala	synonymous_variant	Exon 4 of 4	ENST00000378226.7	NP_055777.1	Q9Y2F9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD3	ENST00000378226.7 link	c.909G>A	p.Ala303Ala	synonymous_variant	Exon 4 of 4	1	NM_014962.4	ENSP00000367471.2		Q9Y2F9-1

Frequencies

GnomAD3 genomes

AF:

0.0538

AC:

8193

AN:

152192

Hom.:

373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0636

Gnomad ASJ

AF:

0.0426

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0181

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0540

GnomAD2 exomes

AF:

0.0734

AC:

18322

AN:

249728

AF XY:

0.0740

show subpopulations

Gnomad AFR exome

AF:

0.0413

Gnomad AMR exome

AF:

0.0845

Gnomad ASJ exome

AF:

0.0528

Gnomad EAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.0214

Gnomad NFE exome

AF:

0.0472

Gnomad OTH exome

AF:

0.0648

GnomAD4 exome

AF:

0.0573

AC:

83738

AN:

1461840

Hom.:

3674

Cov.:

AF XY:

0.0593

AC XY:

43094

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0377

AC:

1261

AN:

33480

American (AMR)

AF:

0.0818

AC:

3660

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0505

AC:

1321

AN:

26136

East Asian (EAS)

AF:

0.253

AC:

10035

AN:

39700

South Asian (SAS)

AF:

0.111

AC:

9549

AN:

86258

European-Finnish (FIN)

AF:

0.0217

AC:

1157

AN:

53368

Middle Eastern (MID)

AF:

0.0742

AC:

428

AN:

5768

European-Non Finnish (NFE)

AF:

0.0472

AC:

52462

AN:

1112010

Other (OTH)

AF:

0.0640

AC:

3865

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

5614

11228

16841

22455

28069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2150

4300

6450

8600

10750

<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:

0.0538

AC:

8193

AN:

152310

Hom.:

369

Cov.:

AF XY:

0.0548

AC XY:

4081

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0385

AC:

1601

AN:

41550

American (AMR)

AF:

0.0637

AC:

975

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0426

AC:

148

AN:

3472

East Asian (EAS)

AF:

0.258

AC:

1335

AN:

5178

South Asian (SAS)

AF:

0.120

AC:

579

AN:

4832

European-Finnish (FIN)

AF:

0.0181

AC:

192

AN:

10622

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0474

AC:

3227

AN:

68030

Other (OTH)

AF:

0.0520

AC:

110

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

397

795

1192

1590

1987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0442

Hom.:

153

Bravo

AF:

0.0580

Asia WGS

AF:

0.165

AC:

575

AN:

3478

EpiCase

AF:

0.0526

EpiControl

AF:

0.0511

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

(source)

DANN

Benign

0.86

PhyloP100

-0.91

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over