6-38350597-C-T

Variant names:

• chr6-38350597-C-T
• rs228188
• NM_001099272.2:c.1155-5504G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099272.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD9	NM_001099272.2	MANE Select	c.1155-5504G>A		intron	N/A	NP_001092742.1	Q96Q07-1
	BTBD9	NM_052893.2		c.1155-5504G>A		intron	N/A	NP_443125.1	Q96Q07-1
	BTBD9	NM_001172418.2		c.1065-5504G>A		intron	N/A	NP_001165889.1	Q96Q07-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD9	ENST00000481247.6	TSL:5 MANE Select	c.1155-5504G>A		intron	N/A	ENSP00000418751.1	Q96Q07-1
	BTBD9	ENST00000419706.6	TSL:1	c.1065-5504G>A		intron	N/A	ENSP00000415365.2	Q96Q07-2
	BTBD9	ENST00000314100.10	TSL:1	c.951-5504G>A		intron	N/A	ENSP00000323408.6	Q96Q07-3

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

African (AFR) AF: 0.912 AC: 37877 AN: 41530

American (AMR) AF: 0.721 AC: 11016 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2242 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4959 AN: 5194

South Asian (SAS) AF: 0.791 AC: 3813 AN: 4818

European-Finnish (FIN) AF: 0.534 AC: 5645 AN: 10578

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36853 AN: 67958

Other (OTH) AF: 0.701 AC: 1479 AN: 2110

Alfa AF: 0.620 Hom.: 24034

Bravo AF: 0.715

Asia WGS AF: 0.888 AC: 3089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.34
DANN	Benign	0.59
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs228188; hg19: chr6-38318373;