rs3733279

Positions:

• chr4-39115625-C-T

Variant summary

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

The ENST00000381930.8(KLHL5):​c.*232C>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 0.569 in 1,368,104 control chromosomes in the GnomAD database, including 223,998 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 (21478 hom., cov: 32)
  • Exomes 𝑓: 0.57 (202520 hom.)
• Consequence: KLHL5 ENST00000381930.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL5	NM_015990.5	c.2073+295C>T		intron_variant		ENST00000504108.7	NP_057074.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL5	ENST00000504108.7	c.2073+295C>T		intron_variant		2	NM_015990.5	ENSP00000423897	A1
	ENST00000668468.1	n.270-46491G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79697 AN: 151402 Hom.: 21463 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.575 AC: 699314 AN: 1216584 Hom.: 202520 Cov.: 31 AF XY: 0.574 AC XY: 336421 AN XY: 586378

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.552

GnomAD4 genome AF: 0.526 AC: 79753 AN: 151520 Hom.: 21478 Cov.: 32 AF XY: 0.527 AC XY: 39023 AN XY: 74054

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.542

Alfa AF: 0.555 Hom.: 3481

Bravo AF: 0.522

Asia WGS AF: 0.513 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.083
DANN	Benign	0.36

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: rs3733279; hg19: chr4-39117245;