13-70066513-T-G

Variant names:

• chr13-70066513-T-G
• rs9317872
• NM_020866.3:c.497+40690A>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+40690A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,118 control chromosomes in the GnomAD database, including 8,410 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 (8410 hom., cov: 32)
• Consequence: KLHL1 NM_020866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL1	NM_020866.3	c.497+40690A>C		intron_variant	Intron 1 of 10	ENST00000377844.9	NP_065917.1
KLHL1	NM_001286725.2	c.497+40690A>C		intron_variant	Intron 1 of 9		NP_001273654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL1	ENST00000377844.9	c.497+40690A>C		intron_variant	Intron 1 of 10	1	NM_020866.3	ENSP00000367075.4
KLHL1	ENST00000545028.2	c.497+40690A>C		intron_variant	Intron 1 of 9	2		ENSP00000439602.2

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45332 AN: 152000 Hom.: 8407 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.298 AC: 45332 AN: 152118 Hom.: 8410 Cov.: 32 AF XY: 0.303 AC XY: 22553 AN XY: 74376

African (AFR) AF: 0.0749 AC: 3110 AN: 41528

American (AMR) AF: 0.329 AC: 5033 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1042 AN: 5174

South Asian (SAS) AF: 0.487 AC: 2348 AN: 4820

European-Finnish (FIN) AF: 0.424 AC: 4479 AN: 10570

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.392 AC: 26675 AN: 67968

Other (OTH) AF: 0.336 AC: 709 AN: 2108

Alfa AF: 0.369 Hom.: 17212

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.52
PhyloP100		1.3
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: rs9317872; hg19: chr13-70640645;