13-70061784-T-G

Variant names:

• chr13-70061784-T-G
• rs12853326
• NM_020866.3:c.497+45419A>C

Variant summary

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

The NM_020866.3(KLHL1):​c.497+45419A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,082 control chromosomes in the GnomAD database, including 8,450 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 0.30 (8450 hom., cov: 32)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 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.497+45419A>C		intron	N/A	NP_065917.1
	KLHL1	NM_001286725.2		c.497+45419A>C		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.497+45419A>C		intron	N/A	ENSP00000367075.4
	KLHL1	ENST00000545028.2	TSL:2	c.497+45419A>C		intron	N/A	ENSP00000439602.2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45713 AN: 151964 Hom.: 8446 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.301 AC: 45722 AN: 152082 Hom.: 8450 Cov.: 32 AF XY: 0.305 AC XY: 22708 AN XY: 74338

African (AFR) AF: 0.0834 AC: 3465 AN: 41538

American (AMR) AF: 0.331 AC: 5046 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1461 AN: 3466

East Asian (EAS) AF: 0.201 AC: 1039 AN: 5176

South Asian (SAS) AF: 0.487 AC: 2349 AN: 4820

European-Finnish (FIN) AF: 0.422 AC: 4454 AN: 10556

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26703 AN: 67948

Other (OTH) AF: 0.336 AC: 708 AN: 2106

Alfa AF: 0.323 Hom.: 1050

Bravo AF: 0.280

Asia WGS AF: 0.334 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.81
PhyloP100		1.2
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: rs12853326; hg19: chr13-70635916;