13-70061784-T-G

Position:

• chr13-70061784-T-G

Variant summary

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

The NM_020866.3(KLHL1):​c.497+45419A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,082 control chromosomes in the GnomAD database, including 8,450 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 (8450 hom., cov: 32)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL1	NM_020866.3	c.497+45419A>C		intron_variant		ENST00000377844.9	NP_065917.1
KLHL1	NM_001286725.2	c.497+45419A>C		intron_variant			NP_001273654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL1	ENST00000377844.9	c.497+45419A>C		intron_variant		1	NM_020866.3	ENSP00000367075	P1
KLHL1	ENST00000545028.2	c.497+45419A>C		intron_variant		2		ENSP00000439602

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45713 AN: 151964 Hom.: 8446 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.301 AC: 45722 AN: 152082 Hom.: 8450 Cov.: 32 AF XY: 0.305 AC XY: 22708 AN XY: 74338

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.336

Alfa AF: 0.323 Hom.: 1050

Bravo AF: 0.280

Asia WGS AF: 0.334 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.81

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: rs12853326; hg19: chr13-70635916;