rs535200

Positions:

• chr2-23646777-G-A

Variant summary

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

The NM_052920.2(KLHL29):​c.940+3927G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,198 control chromosomes in the GnomAD database, including 2,268 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 0.11 (2268 hom., cov: 33)
• Consequence: KLHL29 NM_052920.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL29	NM_052920.2	c.940+3927G>A		intron_variant		ENST00000486442.6	NP_443152.1
KLHL29	XM_006711929.4	c.940+3927G>A		intron_variant			XP_006711992.1
KLHL29	XM_011532501.3	c.22+1673G>A		intron_variant			XP_011530803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL29	ENST00000486442.6	c.940+3927G>A		intron_variant		5	NM_052920.2	ENSP00000420659	P1
KLHL29	ENST00000288548.5	c.459+3927G>A		intron_variant		1		ENSP00000288548

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17235 AN: 152080 Hom.: 2247 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0895

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

GnomAD4 genome AF: 0.114 AC: 17303 AN: 152198 Hom.: 2268 Cov.: 33 AF XY: 0.111 AC XY: 8236 AN XY: 74432

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0144

Gnomad4 NFE AF: 0.0352

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0622 Hom.: 374

Bravo AF: 0.125

Asia WGS AF: 0.0460 AC: 164 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	0.64
DANN	Benign	0.69

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: rs535200; hg19: chr2-23869647;