rs3733275

Positions:

• chr4-39121077-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.*11C>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 0.57 in 1,588,390 control chromosomes in the GnomAD database, including 260,715 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 0.53 (21754 hom., cov: 33)
  • Exomes 𝑓: 0.57 (238961 hom.)
• Consequence: KLHL5 NM_015990.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451

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=-0.9).
• 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.*11C>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.*11C>T		3_prime_UTR_variant	11/11	2	NM_015990.5	ENSP00000423897.2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80222 AN: 151942 Hom.: 21739 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.546

GnomAD3 exomes AF: 0.563 AC: 141286 AN: 250848 Hom.: 40401 AF XY: 0.562 AC XY: 76157 AN XY: 135556

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.646

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.492

Gnomad SAS exome AF: 0.514

Gnomad FIN exome AF: 0.574

Gnomad NFE exome AF: 0.591

Gnomad OTH exome AF: 0.572

GnomAD4 exome AF: 0.574 AC: 824492 AN: 1436330 Hom.: 238961 Cov.: 27 AF XY: 0.573 AC XY: 410078 AN XY: 716028

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.635

Gnomad4 ASJ exome AF: 0.498

Gnomad4 EAS exome AF: 0.525

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.528 AC: 80278 AN: 152060 Hom.: 21754 Cov.: 33 AF XY: 0.529 AC XY: 39319 AN XY: 74358

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.544

Alfa AF: 0.573 Hom.: 46886

Bravo AF: 0.522

Asia WGS AF: 0.514 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3733275; hg19: chr4-39122697; COSMIC: COSV54671301; COSMIC: COSV54671301;