rs11670188

Positions:

• chr19-2014038-A-G

Variant summary

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

The NM_017797.4(BTBD2):​c.407+1259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 149,768 control chromosomes in the GnomAD database, including 2,241 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 0.16 (2232 hom., cov: 27)
  • Exomes 𝑓: 0.23 (9 hom.)
• Consequence: BTBD2 NM_017797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

Genes affected

BTBD2 (HGNC:15504): (BTB domain containing 2) The C-terminus of the protein encoded by this gene binds topoisomerase I. The N-terminus contains a proline-rich region and a BTB/POZ domain (broad-complex, Tramtrack and bric a brac/Pox virus and Zinc finger), both of which are typically involved in protein-protein interactions. Subcellularly, the protein localizes to cytoplasmic bodies. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD2	NM_017797.4	c.407+1259T>C		intron_variant		ENST00000255608.9	NP_060267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD2	ENST00000255608.9	c.407+1259T>C		intron_variant		1	NM_017797.4	ENSP00000255608	P1
	ENST00000615016.1	n.619T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 23776 AN: 149296 Hom.: 2232 Cov.: 27

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.232 AC: 82 AN: 354 Hom.: 9 Cov.: 0 AF XY: 0.235 AC XY: 64 AN XY: 272

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.0385

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.159 AC: 23775 AN: 149414 Hom.: 2232 Cov.: 27 AF XY: 0.158 AC XY: 11481 AN XY: 72832

Gnomad4 AFR AF: 0.0654

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.0984

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.196

Alfa AF: 0.202 Hom.: 4104

Bravo AF: 0.159

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.37

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: rs11670188; hg19: chr19-2014037;