chr2-23675447-C-T

Variant names:

• chr2-23675447-C-T
• rs4665630
• NM_052920.2:c.941-8952C>T

Variant summary

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

The NM_052920.2(KLHL29):​c.941-8952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,062 control chromosomes in the GnomAD database, including 49,922 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 0.79 (49922 hom., cov: 32)
• Consequence: KLHL29 NM_052920.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 14 publications found

Genes affected

KLHL29 (HGNC:29404): (kelch like family member 29)

ENSG00000283031 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL29	NM_052920.2	c.941-8952C>T		intron_variant	Intron 5 of 13	ENST00000486442.6	NP_443152.1
KLHL29	XM_006711929.4	c.941-8952C>T		intron_variant	Intron 4 of 12		XP_006711992.1
KLHL29	XM_011532501.3	c.23-8952C>T		intron_variant	Intron 2 of 10		XP_011530803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL29	ENST00000486442.6	c.941-8952C>T		intron_variant	Intron 5 of 13	5	NM_052920.2	ENSP00000420659.1
KLHL29	ENST00000288548.5	c.458-8952C>T		intron_variant	Intron 1 of 6	1		ENSP00000288548.5
ENSG00000283031	ENST00000634300.1	n.163-2641G>A		intron_variant	Intron 1 of 6	5
ENSG00000283031	ENST00000655321.1	n.163-2641G>A		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120236 AN: 151946 Hom.: 49909 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.791 AC: 120286 AN: 152062 Hom.: 49922 Cov.: 32 AF XY: 0.798 AC XY: 59358 AN XY: 74372

African (AFR) AF: 0.510 AC: 21086 AN: 41372

American (AMR) AF: 0.860 AC: 13151 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3074 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5129 AN: 5178

South Asian (SAS) AF: 0.938 AC: 4526 AN: 4824

European-Finnish (FIN) AF: 0.933 AC: 9906 AN: 10618

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60539 AN: 67994

Other (OTH) AF: 0.831 AC: 1753 AN: 2110

Alfa AF: 0.848 Hom.: 108626

Bravo AF: 0.772

Asia WGS AF: 0.924 AC: 3212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.4
DANN	Benign	0.53
PhyloP100		0.56
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: rs4665630; hg19: chr2-23898317;