13-69945790-C-T

Variant names:

• chr13-69945790-C-T
• rs2225529
• NM_020866.3:c.818-5554G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020866.3(KLHL1):​c.818-5554G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,000 control chromosomes in the GnomAD database, including 1,943 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 0.13 (1943 hom., cov: 32)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL1	NM_020866.3	c.818-5554G>A		intron_variant	Intron 3 of 10	ENST00000377844.9	NP_065917.1
KLHL1	NM_001286725.2	c.635-5554G>A		intron_variant	Intron 2 of 9		NP_001273654.1
KLHL1	XM_017020678.3	c.299-5554G>A		intron_variant	Intron 3 of 10		XP_016876167.1
KLHL1	XM_017020679.2	c.149-5554G>A		intron_variant	Intron 3 of 10		XP_016876168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL1	ENST00000377844.9	c.818-5554G>A		intron_variant	Intron 3 of 10	1	NM_020866.3	ENSP00000367075.4
KLHL1	ENST00000545028.2	c.635-5554G>A		intron_variant	Intron 2 of 9	2		ENSP00000439602.2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19413 AN: 151882 Hom.: 1930 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.128 AC: 19468 AN: 152000 Hom.: 1943 Cov.: 32 AF XY: 0.130 AC XY: 9639 AN XY: 74292

African (AFR) AF: 0.259 AC: 10721 AN: 41438

American (AMR) AF: 0.132 AC: 2010 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1478 AN: 5152

South Asian (SAS) AF: 0.186 AC: 895 AN: 4810

European-Finnish (FIN) AF: 0.0554 AC: 586 AN: 10584

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0496 AC: 3374 AN: 67994

Other (OTH) AF: 0.116 AC: 244 AN: 2106

Alfa AF: 0.0845 Hom.: 1371

Bravo AF: 0.140

Asia WGS AF: 0.251 AC: 871 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.90
DANN	Benign	0.53
PhyloP100		-1.5
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: rs2225529; hg19: chr13-70519922;