rs11647936

Variant names:

• chr16-84651903-A-T
• rs11647936
• NM_024731.4:c.63+973A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024731.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL36	NM_024731.4	MANE Select	c.63+973A>T		intron	N/A	NP_079007.2
	KLHL36	NM_001303451.2		c.63+973A>T		intron	N/A	NP_001290380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL36	ENST00000564996.6	TSL:1 MANE Select	c.63+973A>T		intron	N/A	ENSP00000456743.1
	KLHL36	ENST00000258157.9	TSL:1	c.63+973A>T		intron	N/A	ENSP00000258157.5
	KLHL36	ENST00000569472.5	TSL:2	c.63+973A>T		intron	N/A	ENSP00000455746.1

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

African (AFR) AF: 0.0943 AC: 3918 AN: 41534

American (AMR) AF: 0.269 AC: 4106 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3468

East Asian (EAS) AF: 0.161 AC: 831 AN: 5170

South Asian (SAS) AF: 0.230 AC: 1103 AN: 4806

European-Finnish (FIN) AF: 0.240 AC: 2539 AN: 10594

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20870 AN: 67952

Other (OTH) AF: 0.264 AC: 557 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.39
PhyloP100		-0.15
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: rs11647936; hg19: chr16-84685509;