4-39123253-C-T

Position:

• chr4-39123253-C-T

Variant summary

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

The NM_015990.5(KLHL5):​c.*2187C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,926 control chromosomes in the GnomAD database, including 21,529 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 0.52 (21529 hom., cov: 31)
• Consequence: KLHL5 NM_015990.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

Genes affected

KLHL5 (HGNC:6356): (kelch like family member 5) Predicted to enable actin binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000249207 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL5	NM_015990.5	c.*2187C>T		3_prime_UTR_variant	11/11	ENST00000504108.7	NP_057074.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL5	ENST00000504108.7	c.*2187C>T		3_prime_UTR_variant	11/11	2	NM_015990.5	ENSP00000423897.2

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79707 AN: 151808 Hom.: 21519 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.525 AC: 79750 AN: 151926 Hom.: 21529 Cov.: 31 AF XY: 0.526 AC XY: 39025 AN XY: 74240

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.541

Alfa AF: 0.561 Hom.: 3028

Bravo AF: 0.519

Asia WGS AF: 0.514 AC: 1789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1982009; hg19: chr4-39124873;