13-70060454-C-A

Variant names:

• chr13-70060454-C-A
• rs12871523
• NM_020866.3:c.497+46749G>T

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+46749G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,852 control chromosomes in the GnomAD database, including 7,979 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 0.29 (7979 hom., cov: 31)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	NM_020866.3	MANE Select	c.497+46749G>T		intron	N/A	NP_065917.1
	KLHL1	NM_001286725.2		c.497+46749G>T		intron	N/A	NP_001273654.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	ENST00000377844.9	TSL:1 MANE Select	c.497+46749G>T		intron	N/A	ENSP00000367075.4
	KLHL1	ENST00000545028.2	TSL:2	c.497+46749G>T		intron	N/A	ENSP00000439602.2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44278 AN: 151734 Hom.: 7975 Cov.: 31

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.292 AC: 44277 AN: 151852 Hom.: 7979 Cov.: 31 AF XY: 0.296 AC XY: 21964 AN XY: 74198

African (AFR) AF: 0.0737 AC: 3055 AN: 41448

American (AMR) AF: 0.328 AC: 4995 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3468

East Asian (EAS) AF: 0.198 AC: 1019 AN: 5154

South Asian (SAS) AF: 0.493 AC: 2368 AN: 4808

European-Finnish (FIN) AF: 0.390 AC: 4093 AN: 10504

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26238 AN: 67908

Other (OTH) AF: 0.325 AC: 687 AN: 2114

Alfa AF: 0.201 Hom.: 449

Bravo AF: 0.273

Asia WGS AF: 0.330 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.87
DANN	Benign	0.15
PhyloP100		0.28
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: rs12871523; hg19: chr13-70634586;