11-106070777-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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198439.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD3	NM_198439.3	MANE Select	c.-13+5730A>C		intron	N/A	NP_940841.1
	KBTBD3	NM_152433.4		c.-13+6535A>C		intron	N/A	NP_689646.2
	KBTBD3	NM_001330359.2		c.-5+5730A>C		intron	N/A	NP_001317288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD3	ENST00000531837.2	TSL:1 MANE Select	c.-13+5730A>C		intron	N/A	ENSP00000432163.1
	KBTBD3	ENST00000526793.5	TSL:1	c.-13+6535A>C		intron	N/A	ENSP00000436262.1
	KBTBD3	ENST00000883713.1		c.-13+5727A>C		intron	N/A	ENSP00000553772.1

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 v4.9

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;