rs2273366

Positions:

• chr1-173755803-A-G

Variant summary

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

The NM_014458.4(KLHL20):​c.852-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 611,504 control chromosomes in the GnomAD database, including 21,687 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 0.23 (4436 hom., cov: 32)
  • Exomes 𝑓: 0.27 (17251 hom.)
• Consequence: KLHL20 NM_014458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

Genes affected

KLHL20 (HGNC:25056): (kelch like family member 20) The protein encoded by this gene is a member of the kelch family of proteins, which is characterized by a 44-56 amino acid repeat motif. The kelch motif appears in many different polypeptide contexts and contains multiple potential protein-protein contact sites. Members of this family are present both throughout the cell and extracellularly, with diverse activities. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL20	NM_014458.4	c.852-120A>G		intron_variant		ENST00000209884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL20	ENST00000209884.5	c.852-120A>G		intron_variant		1	NM_014458.4	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34769 AN: 151990 Hom.: 4440 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.269 AC: 123387 AN: 459394 Hom.: 17251 AF XY: 0.269 AC XY: 65291 AN XY: 242940

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.229 AC: 34773 AN: 152110 Hom.: 4436 Cov.: 32 AF XY: 0.227 AC XY: 16869 AN XY: 74362

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.238

Alfa AF: 0.270 Hom.: 3434

Bravo AF: 0.225

Asia WGS AF: 0.241 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.70

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: rs2273366; hg19: chr1-173724942; COSMIC: COSV52940316;