rs4714146

Positions:

• chr6-38320134-G-A

Variant summary

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

The NM_001099272.2(BTBD9):​c.1264+24850C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,256 control chromosomes in the GnomAD database, including 529 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 0.072 (529 hom., cov: 31)
• Consequence: BTBD9 NM_001099272.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD9	NM_001099272.2	c.1264+24850C>T		intron_variant		ENST00000481247.6	NP_001092742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD9	ENST00000481247.6	c.1264+24850C>T		intron_variant		5	NM_001099272.2	ENSP00000418751	P1

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10983 AN: 152138 Hom.: 524 Cov.: 31

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.0914

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0430

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0722 AC: 10989 AN: 152256 Hom.: 529 Cov.: 31 AF XY: 0.0715 AC XY: 5319 AN XY: 74436

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0430

Gnomad4 NFE AF: 0.0892

Gnomad4 OTH AF: 0.0796

Alfa AF: 0.0875 Hom.: 658

Bravo AF: 0.0782

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.39

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: rs4714146; hg19: chr6-38287910;