rs873857

Variant names:

• chr16-84664100-G-C
• rs873857
• NM_024731.4:c.*1967G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 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.*1967G>C		3_prime_UTR	Exon 5 of 5	NP_079007.2
	KLHL36	NM_001303451.2		c.*1967G>C		3_prime_UTR	Exon 4 of 4	NP_001290380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL36	ENST00000564996.6	TSL:1 MANE Select	c.*1967G>C		3_prime_UTR	Exon 5 of 5	ENSP00000456743.1
	KLHL36	ENST00000325279.4	TSL:2	n.2902G>C		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.621 AC: 25736 AN: 41462

American (AMR) AF: 0.532 AC: 8115 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3014 AN: 5162

South Asian (SAS) AF: 0.632 AC: 3052 AN: 4826

European-Finnish (FIN) AF: 0.671 AC: 7074 AN: 10550

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43426 AN: 67948

Other (OTH) AF: 0.612 AC: 1292 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs873857; hg19: chr16-84697706;