6-38473194-A-G

Position:

• chr6-38473194-A-G

Variant summary

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

The NM_001099272.2(BTBD9):​c.1154+104406T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,036 control chromosomes in the GnomAD database, including 8,427 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 0.33 (8427 hom., cov: 32)
• Consequence: BTBD9 NM_001099272.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTBD9	NM_001099272.2	c.1154+104406T>C		intron_variant		ENST00000481247.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD9	ENST00000481247.6	c.1154+104406T>C		intron_variant		5	NM_001099272.2	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49660 AN: 151918 Hom.: 8415 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.327 AC: 49695 AN: 152036 Hom.: 8427 Cov.: 32 AF XY: 0.336 AC XY: 24937 AN XY: 74324

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.350

Alfa AF: 0.321 Hom.: 17501

Bravo AF: 0.321

Asia WGS AF: 0.553 AC: 1922 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3923809; hg19: chr6-38440970;