6-38398410-A-G

Variant names:

• chr6-38398410-A-G
• rs4711546
• NM_001099272.2:c.1155-53317T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099272.2(BTBD9):​c.1155-53317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,964 control chromosomes in the GnomAD database, including 15,967 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 0.41 (15967 hom., cov: 32)
• Consequence: BTBD9 NM_001099272.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD9	NM_001099272.2	c.1155-53317T>C		intron_variant	Intron 6 of 10	ENST00000481247.6	NP_001092742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD9	ENST00000481247.6	c.1155-53317T>C		intron_variant	Intron 6 of 10	5	NM_001099272.2	ENSP00000418751.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62200 AN: 151846 Hom.: 15934 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.410 AC: 62286 AN: 151964 Hom.: 15967 Cov.: 32 AF XY: 0.419 AC XY: 31091 AN XY: 74272

African (AFR) AF: 0.644 AC: 26663 AN: 41402

American (AMR) AF: 0.422 AC: 6443 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 931 AN: 3464

East Asian (EAS) AF: 0.949 AC: 4910 AN: 5176

South Asian (SAS) AF: 0.549 AC: 2641 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3651 AN: 10546

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15824 AN: 67964

Other (OTH) AF: 0.396 AC: 837 AN: 2114

Alfa AF: 0.295 Hom.: 35203

Bravo AF: 0.428

Asia WGS AF: 0.759 AC: 2638 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	10
DANN	Benign	0.82
PhyloP100		0.16
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: rs4711546; hg19: chr6-38366186;