6-96971722-C-T

Variant names:

• chr6-96971722-C-T
• rs974417
• NM_052904.4:c.24-4275C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052904.4. 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
	KLHL32	NM_052904.4	MANE Select	c.24-4275C>T		intron	N/A	NP_443136.2	Q96NJ5-1
	KLHL32	NM_001323252.2		c.24-4275C>T		intron	N/A	NP_001310181.1	Q96NJ5-1
	KLHL32	NM_001286250.2		c.24-4275C>T		intron	N/A	NP_001273179.1	Q96NJ5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL32	ENST00000369261.9	TSL:2 MANE Select	c.24-4275C>T		intron	N/A	ENSP00000358265.4	Q96NJ5-1
	KLHL32	ENST00000951639.1		c.24-4275C>T		intron	N/A	ENSP00000621698.1
	KLHL32	ENST00000536676.5	TSL:2	c.24-4275C>T		intron	N/A	ENSP00000440382.1	Q96NJ5-2

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

African (AFR) AF: 0.342 AC: 14142 AN: 41330

American (AMR) AF: 0.250 AC: 3823 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1007 AN: 5150

South Asian (SAS) AF: 0.266 AC: 1277 AN: 4804

European-Finnish (FIN) AF: 0.164 AC: 1730 AN: 10540

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10248 AN: 67950

Other (OTH) AF: 0.176 AC: 372 AN: 2110

Alfa AF: 0.175 Hom.: 8646

Bravo AF: 0.230

Asia WGS AF: 0.236 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0010
DANN	Benign	0.62
PhyloP100		-1.9
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: rs974417; hg19: chr6-97419598; COSMIC: COSV65111028;