13-69855961-C-T

Variant names:

• chr13-69855961-C-T
• rs2325244
• NM_020866.3:c.1228-16799G>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.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
• 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	NM_020866.3	MANE Select	c.1228-16799G>A		intron	N/A	NP_065917.1	Q9NR64
	KLHL1	NM_001286725.2		c.1045-16799G>A		intron	N/A	NP_001273654.1	F5H1J3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL1	ENST00000377844.9	TSL:1 MANE Select	c.1228-16799G>A		intron	N/A	ENSP00000367075.4	Q9NR64
	KLHL1	ENST00000545028.2	TSL:2	c.1045-16799G>A		intron	N/A	ENSP00000439602.2	F5H1J3

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

African (AFR) AF: 0.279 AC: 11155 AN: 39938

American (AMR) AF: 0.0941 AC: 1358 AN: 14438

Ashkenazi Jewish (ASJ) AF: 0.0812 AC: 280 AN: 3448

East Asian (EAS) AF: 0.000797 AC: 4 AN: 5020

South Asian (SAS) AF: 0.0409 AC: 193 AN: 4722

European-Finnish (FIN) AF: 0.153 AC: 1244 AN: 8146

Middle Eastern (MID) AF: 0.0688 AC: 19 AN: 276

European-Non Finnish (NFE) AF: 0.131 AC: 8742 AN: 66802

Other (OTH) AF: 0.135 AC: 269 AN: 1994

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.074
PhyloP100		-1.0
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: rs2325244; hg19: chr13-70430093;