chr3-183518318-T-G

Position:

• chr3-183518318-T-G

Variant summary

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

The NM_130446.4(KLHL6):​c.459+9527A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,952 control chromosomes in the GnomAD database, including 20,537 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 0.51 (20537 hom., cov: 31)
• Consequence: KLHL6 NM_130446.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

Genes affected

KLHL6 (HGNC:18653): (kelch like family member 6) This gene encodes a member of the kelch-like (KLHL) family of proteins, which is involved in B-lymphocyte antigen receptor signaling and germinal-center B-cell maturation. The encoded protein contains an N-terminal broad-complex, tramtrack and bric a brac (BTB) domain that facilitates protein binding and dimerization, a BTB and C-terminal kelch (BACK) domain, and six C-terminal kelch repeat domains. Naturally occurring mutations in this gene are associated with chronic lymphocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

KLHL6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL6	NM_130446.4	c.459+9527A>C		intron_variant		ENST00000341319.8	NP_569713.2
KLHL6	XM_011513273.4	c.78+9487A>C		intron_variant			XP_011511575.1
KLHL6	XM_011513274.4	c.459+9527A>C		intron_variant			XP_011511576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL6	ENST00000341319.8	c.459+9527A>C		intron_variant		1	NM_130446.4	ENSP00000341342.3
KLHL6	ENST00000468734.1	n.426+9527A>C		intron_variant		1		ENSP00000433734.1
KLHL6	ENST00000489245.5	n.471+9527A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77656 AN: 151834 Hom.: 20513 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.512 AC: 77726 AN: 151952 Hom.: 20537 Cov.: 31 AF XY: 0.509 AC XY: 37823 AN XY: 74242

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.516

Alfa AF: 0.559 Hom.: 48659

Bravo AF: 0.496

Asia WGS AF: 0.422 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.67

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: rs12496193; hg19: chr3-183236106;