rs2252550

Positions:

• chr6-38573708-T-A
• chr6-38573708-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.1154+3892A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,050 control chromosomes in the GnomAD database, including 32,489 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 0.65 (32489 hom., cov: 32)
• Consequence: BTBD9 NM_001099272.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTBD9	NM_001099272.2	c.1154+3892A>T		intron_variant		ENST00000481247.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD9	ENST00000481247.6	c.1154+3892A>T		intron_variant		5	NM_001099272.2	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98664 AN: 151932 Hom.: 32462 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.649 AC: 98740 AN: 152050 Hom.: 32489 Cov.: 32 AF XY: 0.644 AC XY: 47879 AN XY: 74300

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.614

Alfa AF: 0.621 Hom.: 3501

Bravo AF: 0.658

Asia WGS AF: 0.532 AC: 1851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.85
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: rs2252550; hg19: chr6-38541484; COSMIC: COSV58434993; COSMIC: COSV58434993;