rs9592675

Variant names:

• chr13-70063376-C-T
• rs9592675
• NM_020866.3:c.497+43827G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020866.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	NM_020866.3	MANE Select	c.497+43827G>A		intron	N/A	NP_065917.1	Q9NR64
	KLHL1	NM_001286725.2		c.497+43827G>A		intron	N/A	NP_001273654.1	F5H1J3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	ENST00000377844.9	TSL:1 MANE Select	c.497+43827G>A		intron	N/A	ENSP00000367075.4	Q9NR64
	KLHL1	ENST00000545028.2	TSL:2	c.497+43827G>A		intron	N/A	ENSP00000439602.2	F5H1J3

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

African (AFR) AF: 0.0742 AC: 3082 AN: 41514

American (AMR) AF: 0.329 AC: 5017 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1019 AN: 5174

South Asian (SAS) AF: 0.483 AC: 2325 AN: 4812

European-Finnish (FIN) AF: 0.413 AC: 4350 AN: 10524

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26637 AN: 67908

Other (OTH) AF: 0.334 AC: 704 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.40
PhyloP100		-0.24
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: rs9592675; hg19: chr13-70637508;