rs11647936

Positions:

• chr16-84651903-A-T

Variant summary

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

The NM_024731.4(KLHL36):​c.63+973A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,110 control chromosomes in the GnomAD database, including 4,812 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 0.23 (4812 hom., cov: 31)
• Consequence: KLHL36 NM_024731.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

Genes affected

KLHL36 (HGNC:17844): (kelch like family member 36) Enables cullin family protein binding activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL36	NM_024731.4	c.63+973A>T		intron_variant		ENST00000564996.6	NP_079007.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL36	ENST00000564996.6	c.63+973A>T		intron_variant		1	NM_024731.4	ENSP00000456743.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35446 AN: 151992 Hom.: 4811 Cov.: 31

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.233 AC: 35460 AN: 152110 Hom.: 4812 Cov.: 31 AF XY: 0.230 AC XY: 17108 AN XY: 74336

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.264

Alfa AF: 0.257 Hom.: 718

Bravo AF: 0.234

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.39

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: rs11647936; hg19: chr16-84685509;