Genetic Variant BTBD9:c.*757C>A (chr6-38174228-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001099272.2(BTBD9):c.*757C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,138 control chromosomes in the GnomAD database, including 8,606 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 0.31 ( 8605 hom., cov: 33)

Exomes 𝑓: 0.67 ( 1 hom. )

Consequence

BTBD9
NM_001099272.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.601

Publications

9 publications found

Variant links:

Genes affected

BTBD9 (HGNC:21228): (BTB domain containing 9) This locus encodes a BTB/POZ domain-containing protein. This domain is known to be involved in protein-protein interactions. Polymorphisms at this locus have been reported to be associated with susceptibility to Restless Legs Syndrome and may also be associated with Tourette Syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2011]

BTBD9 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=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD9	NM_001099272.2 link	c.*757C>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000481247.6	NP_001092742.1	Q96Q07-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BTBD9	ENST00000481247.6 link	c.*757C>A	3_prime_UTR_variant	Exon 11 of 11	5	NM_001099272.2	ENSP00000418751.1	Q96Q07-1
BTBD9	ENST00000314100.10 link	c.*757C>A	3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000323408.6	Q96Q07-3
BTBD9	ENST00000649492.1 link	c.*757C>A	3_prime_UTR_variant	Exon 12 of 12			ENSP00000497066.1	Q96Q07-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47724

AN:

152014

Hom.:

8602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.335

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.314

AC:

47733

AN:

152132

Hom.:

8605

Cov.:

AF XY:

0.310

AC XY:

23090

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.157

AC:

6500

AN:

41522

American (AMR)

AF:

0.289

AC:

4415

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

1581

AN:

3462

East Asian (EAS)

AF:

0.131

AC:

677

AN:

5180

South Asian (SAS)

AF:

0.321

AC:

1546

AN:

4814

European-Finnish (FIN)

AF:

0.365

AC:

3855

AN:

10576

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.413

AC:

28101

AN:

67974

Other (OTH)

AF:

0.331

AC:

699

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1644

3288

4933

6577

8221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.381

Hom.:

19586

Bravo

AF:

0.296

Asia WGS

AF:

0.192

AC:

667

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.2

(source)

DANN

Benign

0.83

PhyloP100

0.60

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