Genetic Variant BTBD6:p.Asn132Asn (chr14-105249178-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001387567.1(BTBD6):c.396C>T(p.Asn132Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,581,986 control chromosomes in the GnomAD database, including 52,226 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 0.20 ( 3818 hom., cov: 33)

Exomes 𝑓: 0.26 ( 48408 hom. )

Consequence

BTBD6
NM_001387567.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.653

Variant links:

Genes affected

BTBD6 (HGNC:19897): (BTB domain containing 6) Predicted to be involved in neurogenesis. Predicted to be located in cytoplasm. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

BTBD6 links:

BRF1 (HGNC:11551): (BRF1 RNA polymerase III transcription initiation factor subunit) This gene encodes one of the three subunits of the RNA polymerase III transcription factor complex. This complex plays a central role in transcription initiation by RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural RNAs. The gene product belongs to the TF2B family. Several alternatively spliced variants encoding different isoforms, that function at different promoters transcribed by RNA polymerase III, have been identified. [provided by RefSeq, Jun 2011]

BRF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=0.653 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD6	NM_001387567.1 link	c.396C>T	p.Asn132Asn	synonymous_variant	Exon 2 of 4	ENST00000392554.8	NP_001374496.1
BRF1	NM_001519.4 link	c.544+3329G>A		intron_variant	Intron 5 of 17	ENST00000547530.7	NP_001510.2	Q92994-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD6	ENST00000392554.8 link	c.396C>T	p.Asn132Asn	synonymous_variant	Exon 2 of 4	1	NM_001387567.1	ENSP00000376337.4		Q96KE9-3A0A8C8KHP4
BRF1	ENST00000547530.7 link	c.544+3329G>A		intron_variant	Intron 5 of 17	1	NM_001519.4	ENSP00000448387.2		Q92994-1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

30943

AN:

151964

Hom.:

3821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0775

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.274

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.213

GnomAD3 exomes

AF:

0.213

AC:

43303

AN:

203758

Hom.:

4964

AF XY:

0.219

AC XY:

24471

AN XY:

111776

show subpopulations

Gnomad AFR exome

AF:

0.0651

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.115

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.256

AC:

366103

AN:

1429906

Hom.:

48408

Cov.:

AF XY:

0.256

AC XY:

181756

AN XY:

710004

show subpopulations

Gnomad4 AFR exome

AF:

0.0702

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.203

AC:

30938

AN:

152080

Hom.:

3818

Cov.:

AF XY:

0.205

AC XY:

15255

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0775

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.246

Hom.:

4181

Bravo

AF:

0.190

Asia WGS

AF:

0.145

AC:

506

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over