rs9592675

Positions:

• chr13-70063376-C-T

Variant summary

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

The NM_020866.3(KLHL1):​c.497+43827G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,972 control chromosomes in the GnomAD database, including 8,338 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 0.30 (8338 hom., cov: 33)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

Genes affected

KLHL1 (HGNC:6352): (kelch like family member 1) The KLHL1 protein belongs to a family of actin-organizing proteins related to Drosophila Kelch (Nemes et al., 2000 [PubMed 10888605]).[supplied by OMIM, Feb 2010]

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 (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL1	NM_020866.3	c.497+43827G>A		intron_variant		ENST00000377844.9	NP_065917.1
KLHL1	NM_001286725.2	c.497+43827G>A		intron_variant			NP_001273654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL1	ENST00000377844.9	c.497+43827G>A		intron_variant		1	NM_020866.3	ENSP00000367075	P1
KLHL1	ENST00000545028.2	c.497+43827G>A		intron_variant		2		ENSP00000439602

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45085 AN: 151856 Hom.: 8335 Cov.: 33

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.297 AC: 45084 AN: 151972 Hom.: 8338 Cov.: 33 AF XY: 0.301 AC XY: 22393 AN XY: 74288

Gnomad4 AFR AF: 0.0742

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.334

Alfa AF: 0.321 Hom.: 1047

Bravo AF: 0.277

Asia WGS AF: 0.326 AC: 1129 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.40

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: rs9592675; hg19: chr13-70637508;