Variant 4-39113015-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015990.5(KLHL5):c.1689-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00733 in 1,611,144 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 73 hom. )

Consequence

KLHL5
NM_015990.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002957

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Variant links:

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]

KLHL5 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-39113015-T-C is Benign according to our data. Variant chr4-39113015-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2654727.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL5	NM_015990.5 linkuse as main transcript	c.1689-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000504108.7	NP_057074.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL5	ENST00000504108.7 linkuse as main transcript	c.1689-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_015990.5	ENSP00000423897	A1	Q96PQ7-6
	ENST00000668468.1 linkuse as main transcript	n.270-43881A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

781

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00725

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00855

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00604

AC:

1513

AN:

250538

Hom.:

AF XY:

0.00596

AC XY:

808

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00304

Gnomad FIN exome

AF:

0.00921

Gnomad NFE exome

AF:

0.00974

Gnomad OTH exome

AF:

0.00345

GnomAD4 exome

AF:

0.00756

AC:

11030

AN:

1458792

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

5392

AN XY:

725890

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00324

Gnomad4 FIN exome

AF:

0.00867

Gnomad4 NFE exome

AF:

0.00879

Gnomad4 OTH exome

AF:

0.00601

GnomAD4 genome

AF:

0.00514

AC:

783

AN:

152352

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00725

Gnomad4 NFE

AF:

0.00857

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00681

Hom.:

Bravo

AF:

0.00457

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

KLHL5: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.2

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000030

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over