rs3764628

Variant names:

• chr19-18636795-G-T
• rs3764628
• NM_018316.3:c.-260G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018316.3(KLHL26):​c.-260G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 149,956 control chromosomes in the GnomAD database, including 926 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 0.10 (926 hom., cov: 30)
• Consequence: KLHL26 NM_018316.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794
• Publications: 25 publications found

Genes affected

KLHL26 (HGNC:25623): (kelch like family member 26)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL26	NM_018316.3	c.-260G>T		upstream_gene_variant		ENST00000300976.9	NP_060786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL26	ENST00000300976.9	c.-260G>T		upstream_gene_variant		1	NM_018316.3	ENSP00000300976.3
KLHL26	ENST00000599006.5	c.-260G>T		upstream_gene_variant		5		ENSP00000472001.1
KLHL26	ENST00000595182.5	c.-260G>T		upstream_gene_variant		4		ENSP00000472032.1
KLHL26	ENST00000600657.5	n.-260G>T		upstream_gene_variant		4		ENSP00000470999.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15073 AN: 149838 Hom.: 927 Cov.: 30

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0927

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0683

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.101 AC: 15074 AN: 149956 Hom.: 926 Cov.: 30 AF XY: 0.0996 AC XY: 7290 AN XY: 73208

African (AFR) AF: 0.0280 AC: 1139 AN: 40716

American (AMR) AF: 0.0927 AC: 1399 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3452

East Asian (EAS) AF: 0.108 AC: 536 AN: 4948

South Asian (SAS) AF: 0.0350 AC: 165 AN: 4714

European-Finnish (FIN) AF: 0.161 AC: 1678 AN: 10408

Middle Eastern (MID) AF: 0.0659 AC: 17 AN: 258

European-Non Finnish (NFE) AF: 0.138 AC: 9331 AN: 67404

Other (OTH) AF: 0.105 AC: 217 AN: 2070

Alfa AF: 0.124 Hom.: 5836

Bravo AF: 0.0942

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.78
PhyloP100		-0.79
PromoterAI		-0.027	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3764628; hg19: chr19-18747605;