rs978026

chr13-70025307-T-C

Variant summary

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

The NM_020866.3(KLHL1):c.498-49505A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,006 control chromosomes in the GnomAD database, including 53,114 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 0.83 (53114 hom., cov: 32)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

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 (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL1	NM_020866.3	c.498-49505A>G		intron_variant		ENST00000377844.9
KLHL1	NM_001286725.2	c.498-63863A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL1	ENST00000377844.9	c.498-49505A>G		intron_variant		1	NM_020866.3	P1
KLHL1	ENST00000545028.2	c.498-63863A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125962 AN: 151888 Hom.: 53074 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.829 AC: 126058 AN: 152006 Hom.: 53114 Cov.: 32 AF XY: 0.831 AC XY: 61717 AN XY: 74292

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.857

Alfa AF: 0.885 Hom.: 123140

Bravo AF: 0.827

Asia WGS AF: 0.886 AC: 3079 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.39
Dann	Benign	0.51

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: rs978026; hg19: chr13-70599439;