rs12196956

Variant names:

• chr6-38175619-G-A
• rs12196956
• NM_001099272.2:c.1642-437C>T

Variant summary

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

The NM_001099272.2(BTBD9):​c.1642-437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,194 control chromosomes in the GnomAD database, including 786 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 0.087 (786 hom., cov: 33)
• Consequence: BTBD9 NM_001099272.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 2 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]

LOC124901315 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD9	NM_001099272.2	c.1642-437C>T		intron_variant	Intron 10 of 10	ENST00000481247.6	NP_001092742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD9	ENST00000481247.6	c.1642-437C>T		intron_variant	Intron 10 of 10	5	NM_001099272.2	ENSP00000418751.1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13300 AN: 152076 Hom.: 787 Cov.: 33

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0940

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

GnomAD4 genome AF: 0.0874 AC: 13296 AN: 152194 Hom.: 786 Cov.: 33 AF XY: 0.0891 AC XY: 6629 AN XY: 74406

African (AFR) AF: 0.0218 AC: 905 AN: 41538

American (AMR) AF: 0.0871 AC: 1332 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3472

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5186

South Asian (SAS) AF: 0.0615 AC: 296 AN: 4816

European-Finnish (FIN) AF: 0.168 AC: 1773 AN: 10562

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8271 AN: 68010

Other (OTH) AF: 0.0935 AC: 197 AN: 2108

Alfa AF: 0.103 Hom.: 674

Bravo AF: 0.0765

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.82
PhyloP100		-0.13
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: rs12196956; hg19: chr6-38143395;