rs1046655

Positions:

• chr4-39126127-G-A

Variant summary

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

The NM_015990.5(KLHL5):​c.*5061G>A 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 151,984 control chromosomes in the GnomAD database, including 21,556 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 (21556 hom., cov: 32)
• Consequence: KLHL5 NM_015990.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499

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 = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL5	NM_015990.5	c.*5061G>A		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.*5061G>A		3_prime_UTR_variant	11/11	2	NM_015990.5	ENSP00000423897	A1
	ENST00000668468.1	n.269+51491C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79781 AN: 151866 Hom.: 21546 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.525 AC: 79826 AN: 151984 Hom.: 21556 Cov.: 32 AF XY: 0.526 AC XY: 39062 AN XY: 74294

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.542

Alfa AF: 0.471 Hom.: 2003

Bravo AF: 0.519

Asia WGS AF: 0.513 AC: 1785 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	0.96
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1046655; hg19: chr4-39127747;