6-38350597-C-T

Variant summary

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

The NM_001099272.2(BTBD9):c.1155-5504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,148 control chromosomes in the GnomAD database, including 38,092 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 0.69 (38092 hom., cov: 33)
• Consequence: BTBD9 NM_001099272.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTBD9	NM_001099272.2	c.1155-5504G>A		intron_variant		ENST00000481247.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD9	ENST00000481247.6	c.1155-5504G>A		intron_variant		5	NM_001099272.2	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104542 AN: 152030 Hom.: 38021 Cov.: 33

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.688 AC: 104669 AN: 152148 Hom.: 38092 Cov.: 33 AF XY: 0.691 AC XY: 51413 AN XY: 74382

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.701

Alfa AF: 0.605 Hom.: 15696

Bravo AF: 0.715

Asia WGS AF: 0.888 AC: 3089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.34
Dann	Benign	0.59

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: rs228188; hg19: chr6-38318373;