rs1330628

Variant names:

• chr6-96908248-G-A
• rs1330628
• NM_001323258.2:c.-66+7846G>A

Variant summary

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

The NM_001323258.2(KLHL32):​c.-66+7846G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,086 control chromosomes in the GnomAD database, including 6,071 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 0.28 (6071 hom., cov: 32)
• Consequence: KLHL32 NM_001323258.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 1 publications found

Genes affected

KLHL32 (HGNC:21221): (kelch like family member 32)

ENSG00000299332 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL32	NM_001323258.2	c.-66+7846G>A		intron_variant	Intron 2 of 7		NP_001310187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000299332	ENST00000762683.1	n.381+2702G>A		intron_variant	Intron 3 of 3
ENSG00000299332	ENST00000762684.1	n.372-590G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42744 AN: 151968 Hom.: 6062 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.281 AC: 42783 AN: 152086 Hom.: 6071 Cov.: 32 AF XY: 0.284 AC XY: 21114 AN XY: 74342

African (AFR) AF: 0.301 AC: 12495 AN: 41494

American (AMR) AF: 0.303 AC: 4625 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5176

South Asian (SAS) AF: 0.318 AC: 1532 AN: 4820

European-Finnish (FIN) AF: 0.271 AC: 2862 AN: 10570

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18198 AN: 67954

Other (OTH) AF: 0.258 AC: 544 AN: 2112

Alfa AF: 0.271 Hom.: 687

Bravo AF: 0.283

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.081
DANN	Benign	0.69
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1330628; hg19: chr6-97356124; COSMIC: COSV69414928;