Variant chr22-50548313-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138433.5(KLHDC7B):c.2070A>G(p.Ile690Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,551,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

KLHDC7B
NM_138433.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.245

Variant links:

Genes affected

KLHDC7B (HGNC:25145): (kelch domain containing 7B)

KLHDC7B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023652285).

BP6

Variant 22-50548313-A-G is Benign according to our data. Variant chr22-50548313-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2350989.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7B	NM_138433.5 linkuse as main transcript	c.2070A>G	p.Ile690Met	missense_variant	1/1	ENST00000648057.3	NP_612442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC7B	ENST00000648057.3 linkuse as main transcript	c.2070A>G	p.Ile690Met	missense_variant	1/1		NM_138433.5	ENSP00000497256	P3
KLHDC7B	ENST00000395676.4 linkuse as main transcript	c.147A>G	p.Ile49Met	missense_variant	1/1			ENSP00000379034	A2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000211

AC:

AN:

156166

Hom.:

AF XY:

0.000217

AC XY:

AN XY:

82816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.000707

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000332

Gnomad OTH exome

AF:

0.000456

GnomAD4 exome

AF:

0.000192

AC:

268

AN:

1398980

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

121

AN XY:

690008

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.000252

Gnomad4 ASJ exome

AF:

0.000874

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000202

Gnomad4 OTH exome

AF:

0.000207

GnomAD4 genome

AF:

0.000158

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000411

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000549

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.9

DANN

Benign

0.36

DEOGEN2

Benign

0.0017

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.12

T;T

M_CAP

Benign

0.077

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.34

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

0.45

.;N

REVEL

Benign

0.14

Sift

Benign

0.25

.;T

Sift4G

Benign

0.31

.;T

Polyphen

0.0

.;B

Vest4

0.013

MVP

0.36

ClinPred

0.030

GERP RS

-0.047

Varity_R

0.054

gMVP

0.052

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