NM_052904.4:c.412-2156T>C

Variant names:

• chr6-97082970-T-C
• rs9320409
• NM_052904.4:c.412-2156T>C

Variant summary

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

The NM_052904.4(KLHL32):​c.412-2156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,060 control chromosomes in the GnomAD database, including 11,073 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 0.36 (11073 hom., cov: 32)
• Consequence: KLHL32 NM_052904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL32	NM_052904.4	c.412-2156T>C		intron_variant	Intron 5 of 10	ENST00000369261.9	NP_443136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL32	ENST00000369261.9	c.412-2156T>C		intron_variant	Intron 5 of 10	2	NM_052904.4	ENSP00000358265.4

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55093 AN: 151942 Hom.: 11072 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.362 AC: 55095 AN: 152060 Hom.: 11073 Cov.: 32 AF XY: 0.362 AC XY: 26913 AN XY: 74332

African (AFR) AF: 0.181 AC: 7528 AN: 41488

American (AMR) AF: 0.308 AC: 4713 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1620 AN: 3464

East Asian (EAS) AF: 0.457 AC: 2356 AN: 5160

South Asian (SAS) AF: 0.400 AC: 1927 AN: 4818

European-Finnish (FIN) AF: 0.467 AC: 4939 AN: 10570

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30638 AN: 67960

Other (OTH) AF: 0.387 AC: 815 AN: 2106

Alfa AF: 0.423 Hom.: 8343

Bravo AF: 0.345

Asia WGS AF: 0.385 AC: 1340 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	8.9
DANN	Benign	0.66
PhyloP100		1.1
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: rs9320409; hg19: chr6-97530846;