rs3733279

Variant names:

• chr4-39115625-C-T
• rs3733279
• ENST00000381930.8:c.*232C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381930.8. 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.2073+295C>T		intron	N/A	NP_057074.4
	KLHL5	NM_001007075.2		c.2073+295C>T		intron	N/A	NP_001007076.1	Q7Z6D5
	KLHL5	NM_199039.4		c.1890+295C>T		intron	N/A	NP_950240.3	A0A804C9D6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL5	ENST00000381930.8	TSL:1	c.*232C>T		3_prime_UTR	Exon 10 of 10	ENSP00000371355.4	A0A804CHP1
	KLHL5	ENST00000504108.7	TSL:2 MANE Select	c.2073+295C>T		intron	N/A	ENSP00000423897.2	Q96PQ7-6
	KLHL5	ENST00000261425.7	TSL:1	c.2073+295C>T		intron	N/A	ENSP00000261425.3	Q96PQ7-6

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

African (AFR) AF: 0.376 AC: 9688 AN: 25756

American (AMR) AF: 0.596 AC: 8287 AN: 13898

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 8709 AN: 17578

East Asian (EAS) AF: 0.524 AC: 15728 AN: 30010

South Asian (SAS) AF: 0.505 AC: 25171 AN: 49822

European-Finnish (FIN) AF: 0.583 AC: 14826 AN: 25452

Middle Eastern (MID) AF: 0.529 AC: 1790 AN: 3384

European-Non Finnish (NFE) AF: 0.587 AC: 587378 AN: 1000454

Other (OTH) AF: 0.552 AC: 27737 AN: 50230

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

African (AFR) AF: 0.390 AC: 16131 AN: 41322

American (AMR) AF: 0.589 AC: 8983 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1708 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2525 AN: 5162

South Asian (SAS) AF: 0.520 AC: 2507 AN: 4824

European-Finnish (FIN) AF: 0.570 AC: 5958 AN: 10450

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.594 AC: 40230 AN: 67750

Other (OTH) AF: 0.542 AC: 1142 AN: 2108

Alfa AF: 0.549 Hom.: 3548

Bravo AF: 0.522

Asia WGS AF: 0.513 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.083
DANN	Benign	0.36
PhyloP100		-1.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3733279;

hg19: chr4-39117245;