rs974417

Positions:

• chr6-96971722-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052904.4(KLHL32):​c.24-4275C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,820 control chromosomes in the GnomAD database, including 4,156 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 0.22 (4156 hom., cov: 32)
• Consequence: KLHL32 NM_052904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

Genes affected

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

KLHL32 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL32	NM_052904.4	c.24-4275C>T		intron_variant		ENST00000369261.9	NP_443136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL32	ENST00000369261.9	c.24-4275C>T		intron_variant		2	NM_052904.4	ENSP00000358265.4

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33284 AN: 151702 Hom.: 4153 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.219 AC: 33317 AN: 151820 Hom.: 4156 Cov.: 32 AF XY: 0.221 AC XY: 16409 AN XY: 74222

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.176

Alfa AF: 0.161 Hom.: 4328

Bravo AF: 0.230

Asia WGS AF: 0.236 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0010
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs974417; hg19: chr6-97419598; COSMIC: COSV65111028;