Variant chr7-23125082-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001031710.3(KLHL7):c.352C>T(p.Leu118Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,610,180 control chromosomes in the GnomAD database, including 115,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15691 hom., cov: 32)

Exomes 𝑓: 0.36 ( 99638 hom. )

Consequence

KLHL7
NM_001031710.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

KLHL7 (HGNC:15646): (kelch like family member 7) This gene encodes a BTB-Kelch-related protein. The encoded protein may be involved in protein degradation. Mutations in this gene have been associated with retinitis pigmentosa 42. [provided by RefSeq, Feb 2010]

KLHL7 links:

KLHL7 (HGNC:):

KLHL7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 7-23125082-C-T is Benign according to our data. Variant chr7-23125082-C-T is described in ClinVar as [Benign]. Clinvar id is 359798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL7	NM_001031710.3 linkuse as main transcript	c.352C>T	p.Leu118Leu	synonymous_variant	4/11	ENST00000339077.10	NP_001026880.2	Q8IXQ5-1A8K364

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL7	ENST00000339077.10 linkuse as main transcript	c.352C>T	p.Leu118Leu	synonymous_variant	4/11	1	NM_001031710.3	ENSP00000343273.4		Q8IXQ5-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65747

AN:

151950

Hom.:

15658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.642

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.345

AC:

86522

AN:

251008

Hom.:

16327

AF XY:

0.341

AC XY:

46247

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.651

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.373

Gnomad OTH exome

AF:

0.352

GnomAD4 exome

AF:

0.363

AC:

530014

AN:

1458112

Hom.:

99638

Cov.:

AF XY:

0.360

AC XY:

261264

AN XY:

725482

show subpopulations

Gnomad4 AFR exome

AF:

0.654

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.374

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.371

Gnomad4 OTH exome

AF:

0.379

GnomAD4 genome

AF:

0.433

AC:

65824

AN:

152068

Hom.:

15691

Cov.:

AF XY:

0.424

AC XY:

31495

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.642

Gnomad4 AMR

AF:

0.341

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.374

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.385

Hom.:

27028

Bravo

AF:

0.445

Asia WGS

AF:

0.362

AC:

1256

AN:

3472

EpiCase

AF:

0.382

EpiControl

AF:

0.381

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

PERCHING syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

8.2

DANN

Benign

0.80

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

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