rs12871523

chr13-70060454-C-Achr13-70060454-C-Gchr13-70060454-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+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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL1	NM_020866.3	c.497+46749G>T		intron_variant		ENST00000377844.9
KLHL1	NM_001286725.2	c.497+46749G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL1	ENST00000377844.9	c.497+46749G>T		intron_variant		1	NM_020866.3	P1
KLHL1	ENST00000545028.2	c.497+46749G>T		intron_variant		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

Gnomad4 AFR AF: 0.0737

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.325

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.87
Dann	Benign	0.15

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: rs12871523; hg19: chr13-70634586;