NM_020866.3:c.1015-135T>G

Variant names:

• chr13-69882630-A-C
• rs10507774
• NM_020866.3:c.1015-135T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020866.3(KLHL1):​c.1015-135T>G variant causes a intron change. The variant allele was found at a frequency of 0.0278 in 629,932 control chromosomes in the GnomAD database, including 883 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 0.057 (640 hom., cov: 32)
  • Exomes 𝑓: 0.018 (243 hom.)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020866.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	NM_020866.3	MANE Select	c.1015-135T>G		intron	N/A	NP_065917.1
	KLHL1	NM_001286725.2		c.832-135T>G		intron	N/A	NP_001273654.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	ENST00000377844.9	TSL:1 MANE Select	c.1015-135T>G		intron	N/A	ENSP00000367075.4
	KLHL1	ENST00000545028.2	TSL:2	c.832-135T>G		intron	N/A	ENSP00000439602.2

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8704 AN: 152152 Hom.: 630 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0473

GnomAD4 exome AF: 0.0184 AC: 8769 AN: 477662 Hom.: 243 AF XY: 0.0167 AC XY: 4224 AN XY: 252308

African (AFR) AF: 0.160 AC: 2077 AN: 12974

American (AMR) AF: 0.0206 AC: 409 AN: 19816

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 186 AN: 14124

East Asian (EAS) AF: 0.0000318 AC: 1 AN: 31434

South Asian (SAS) AF: 0.00283 AC: 129 AN: 45654

European-Finnish (FIN) AF: 0.0173 AC: 549 AN: 31706

Middle Eastern (MID) AF: 0.0227 AC: 46 AN: 2028

European-Non Finnish (NFE) AF: 0.0160 AC: 4677 AN: 292828

Other (OTH) AF: 0.0256 AC: 695 AN: 27098

GnomAD4 genome AF: 0.0574 AC: 8738 AN: 152270 Hom.: 640 Cov.: 32 AF XY: 0.0551 AC XY: 4103 AN XY: 74460

African (AFR) AF: 0.167 AC: 6941 AN: 41524

American (AMR) AF: 0.0246 AC: 377 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4828

European-Finnish (FIN) AF: 0.0190 AC: 202 AN: 10626

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1039 AN: 68020

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0440 Hom.: 57

Bravo AF: 0.0639

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.77
PhyloP100		3.7
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: rs10507774; hg19: chr13-70456762;