rs9296249

Positions:

• chr6-38398065-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099272.2(BTBD9):​c.1155-52972A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,008 control chromosomes in the GnomAD database, including 7,702 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 0.30 (7702 hom., cov: 32)
• Consequence: BTBD9 NM_001099272.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD9	NM_001099272.2	c.1155-52972A>G		intron_variant		ENST00000481247.6	NP_001092742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD9	ENST00000481247.6	c.1155-52972A>G		intron_variant		5	NM_001099272.2	ENSP00000418751	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46311 AN: 151890 Hom.: 7685 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.305 AC: 46355 AN: 152008 Hom.: 7702 Cov.: 32 AF XY: 0.311 AC XY: 23079 AN XY: 74312

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.307

Alfa AF: 0.251 Hom.: 9193

Bravo AF: 0.312

Asia WGS AF: 0.451 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs9296249; hg19: chr6-38365841;