chr11-106070777-T-G

Variant names:

• chr11-106070777-T-G
• rs11226914
• NM_198439.3:c.-13+5730A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_198439.3(KBTBD3):​c.-13+5730A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 152,214 control chromosomes in the GnomAD database, including 28 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 0.012 (28 hom., cov: 33)
• Consequence: KBTBD3 NM_198439.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 1 publications found

Genes affected

KBTBD3 (HGNC:22934): (kelch repeat and BTB domain containing 3)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0117 (1780/152214) while in subpopulation AMR AF = 0.0196 (299/15292). AF 95% confidence interval is 0.0177. There are 28 homozygotes in GnomAd4. There are 828 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD3	NM_198439.3	c.-13+5730A>C		intron_variant	Intron 2 of 3	ENST00000531837.2	NP_940841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD3	ENST00000531837.2	c.-13+5730A>C		intron_variant	Intron 2 of 3	1	NM_198439.3	ENSP00000432163.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1779 AN: 152096 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.00330

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0117 AC: 1780 AN: 152214 Hom.: 28 Cov.: 33 AF XY: 0.0111 AC XY: 828 AN XY: 74422

African (AFR) AF: 0.00329 AC: 137 AN: 41580

American (AMR) AF: 0.0196 AC: 299 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4828

European-Finnish (FIN) AF: 0.00283 AC: 30 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0167 AC: 1134 AN: 67920

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0148 Hom.: 27

Bravo AF: 0.0131

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.74
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism

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: rs11226914; hg19: chr11-105941504;