NM_015483.3:c.-338-2277C>T

Variant names:

• chr7-32882219-G-A
• rs6462430
• NM_015483.3:c.-338-2277C>T

Variant summary

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

The NM_015483.3(KBTBD2):​c.-338-2277C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,872 control chromosomes in the GnomAD database, including 19,434 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 0.48 (19434 hom., cov: 31)
• Consequence: KBTBD2 NM_015483.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 7 publications found

Genes affected

KBTBD2 (HGNC:21751): (kelch repeat and BTB domain containing 2) Predicted to act upstream of or within with a positive effect on several processes, including glucose metabolic process; phosphatidylinositol 3-kinase signaling; and response to insulin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD2	NM_015483.3	c.-338-2277C>T		intron_variant	Intron 1 of 3	ENST00000304056.9	NP_056298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD2	ENST00000304056.9	c.-338-2277C>T		intron_variant	Intron 1 of 3	1	NM_015483.3	ENSP00000302586.4

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73448 AN: 151756 Hom.: 19417 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.484 AC: 73506 AN: 151872 Hom.: 19434 Cov.: 31 AF XY: 0.481 AC XY: 35671 AN XY: 74206

African (AFR) AF: 0.710 AC: 29383 AN: 41412

American (AMR) AF: 0.342 AC: 5209 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2532 AN: 5168

South Asian (SAS) AF: 0.558 AC: 2684 AN: 4806

European-Finnish (FIN) AF: 0.389 AC: 4097 AN: 10524

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26767 AN: 67932

Other (OTH) AF: 0.487 AC: 1027 AN: 2110

Alfa AF: 0.454 Hom.: 2249

Bravo AF: 0.487

Asia WGS AF: 0.530 AC: 1839 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.15
PhyloP100		-0.037
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: rs6462430; hg19: chr7-32921831;