13-69855961-C-T

Position:

• chr13-69855961-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.1228-16799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 145,682 control chromosomes in the GnomAD database, including 2,378 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 0.16 (2378 hom., cov: 30)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL1	NM_020866.3	c.1228-16799G>A		intron_variant		ENST00000377844.9	NP_065917.1
KLHL1	NM_001286725.2	c.1045-16799G>A		intron_variant			NP_001273654.1
KLHL1	XM_017020678.3	c.709-16799G>A		intron_variant			XP_016876167.1
KLHL1	XM_017020679.2	c.559-16799G>A		intron_variant			XP_016876168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL1	ENST00000377844.9	c.1228-16799G>A		intron_variant		1	NM_020866.3	ENSP00000367075.4
KLHL1	ENST00000545028.2	c.1045-16799G>A		intron_variant		2		ENSP00000439602.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 23350 AN: 145684 Hom.: 2373 Cov.: 30

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0812

Gnomad EAS AF: 0.000794

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0767

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.160 AC: 23369 AN: 145682 Hom.: 2378 Cov.: 30 AF XY: 0.157 AC XY: 11069 AN XY: 70710

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.0941

Gnomad4 ASJ AF: 0.0812

Gnomad4 EAS AF: 0.000797

Gnomad4 SAS AF: 0.0409

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.135

Alfa AF: 0.150 Hom.: 233

Bravo AF: 0.162

Asia WGS AF: 0.0490 AC: 167 AN: 3388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.074

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: rs2325244; hg19: chr13-70430093;