rs3733275

Variant names:

• chr4-39121077-C-T
• rs3733275
• NM_015990.5:c.*11C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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:58761):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015990.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL5	NM_015990.5	MANE Select	c.*11C>T		3_prime_UTR	Exon 11 of 11	NP_057074.4
	KLHL5	NM_001007075.2		c.*11C>T		3_prime_UTR	Exon 12 of 12	NP_001007076.1
	KLHL5	NM_199039.4		c.*11C>T		3_prime_UTR	Exon 10 of 10	NP_950240.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL5	ENST00000504108.7	TSL:2 MANE Select	c.*11C>T		3_prime_UTR	Exon 11 of 11	ENSP00000423897.2
	KLHL5	ENST00000261425.7	TSL:1	c.*11C>T		3_prime_UTR	Exon 12 of 12	ENSP00000261425.3
	KLHL5	ENST00000261426.10	TSL:1	c.*11C>T		3_prime_UTR	Exon 10 of 10	ENSP00000261426.6

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

GnomAD2 exomes AF: 0.563 AC: 141286 AN: 250848 AF XY: 0.562

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 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

African (AFR) AF: 0.383 AC: 12659 AN: 33070

American (AMR) AF: 0.635 AC: 28375 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 12924 AN: 25974

East Asian (EAS) AF: 0.525 AC: 20805 AN: 39614

South Asian (SAS) AF: 0.513 AC: 43874 AN: 85602

European-Finnish (FIN) AF: 0.581 AC: 31034 AN: 53378

Middle Eastern (MID) AF: 0.510 AC: 2759 AN: 5406

European-Non Finnish (NFE) AF: 0.587 AC: 639108 AN: 1089092

Other (OTH) AF: 0.553 AC: 32954 AN: 59540

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

African (AFR) AF: 0.392 AC: 16243 AN: 41442

American (AMR) AF: 0.590 AC: 9030 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3472

East Asian (EAS) AF: 0.491 AC: 2541 AN: 5176

South Asian (SAS) AF: 0.520 AC: 2507 AN: 4818

European-Finnish (FIN) AF: 0.575 AC: 6079 AN: 10572

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40440 AN: 67964

Other (OTH) AF: 0.544 AC: 1149 AN: 2112

Alfa AF: 0.568 Hom.: 99539

Bravo AF: 0.522

Asia WGS AF: 0.514 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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