rs873857

Positions:

• chr16-84664100-G-C

Variant summary

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

The NM_024731.4(KLHL36):​c.*1967G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,008 control chromosomes in the GnomAD database, including 29,699 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 0.62 (29699 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: KLHL36 NM_024731.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL36	NM_024731.4	c.*1967G>C		3_prime_UTR_variant	5/5	ENST00000564996.6	NP_079007.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL36	ENST00000564996.6	c.*1967G>C		3_prime_UTR_variant	5/5	1	NM_024731.4	ENSP00000456743.1
KLHL36	ENST00000325279.4	n.2902G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94625 AN: 151888 Hom.: 29669 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.623 AC: 94700 AN: 152006 Hom.: 29699 Cov.: 32 AF XY: 0.623 AC XY: 46280 AN XY: 74282

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.612

Alfa AF: 0.628 Hom.: 3722

Bravo AF: 0.615

Asia WGS AF: 0.613 AC: 2136 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	1.8
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs873857; hg19: chr16-84697706;