Genetic Variant KLHDC7B:p.Val1130Val (chr22-50549633-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_138433.5(KLHDC7B):c.3390G>T(p.Val1130Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,555,092 control chromosomes in the GnomAD database, including 177,356 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 0.42 ( 14423 hom., cov: 34)

Exomes 𝑓: 0.48 ( 162933 hom. )

Consequence

KLHDC7B
NM_138433.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71

Publications

19 publications found

Variant links:

Genes affected

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

KLHDC7B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP7

Synonymous conserved (PhyloP=2.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC7B	NM_138433.5 link	c.3390G>T	p.Val1130Val	synonymous_variant	Exon 1 of 1	ENST00000648057.3	NP_612442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC7B	ENST00000648057.3 link	c.3390G>T	p.Val1130Val	synonymous_variant	Exon 1 of 1		NM_138433.5	ENSP00000497256.1
KLHDC7B	ENST00000395676.4 link	c.1467G>T	p.Val489Val	synonymous_variant	Exon 1 of 1	6		ENSP00000379034.2

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63342

AN:

151942

Hom.:

14418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.405

GnomAD2 exomes

AF:

0.478

AC:

99946

AN:

209046

AF XY:

0.479

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.467

Gnomad EAS exome

AF:

0.629

Gnomad FIN exome

AF:

0.589

Gnomad NFE exome

AF:

0.492

Gnomad OTH exome

AF:

0.477

GnomAD4 exome

AF:

0.478

AC:

671071

AN:

1403030

Hom.:

162933

Cov.:

AF XY:

0.476

AC XY:

328499

AN XY:

690210

show subpopulations

African (AFR)

AF:

0.206

AC:

6658

AN:

32246

American (AMR)

AF:

0.467

AC:

18718

AN:

40042

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

10057

AN:

22330

East Asian (EAS)

AF:

0.615

AC:

24056

AN:

39084

South Asian (SAS)

AF:

0.408

AC:

31724

AN:

77748

European-Finnish (FIN)

AF:

0.576

AC:

28140

AN:

48844

Middle Eastern (MID)

AF:

0.388

AC:

2122

AN:

5464

European-Non Finnish (NFE)

AF:

0.485

AC:

523275

AN:

1079500

Other (OTH)

AF:

0.456

AC:

26321

AN:

57772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

24339

48678

73018

97357

121696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15742

31484

47226

62968

78710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.417

AC:

63357

AN:

152062

Hom.:

14423

Cov.:

AF XY:

0.423

AC XY:

31451

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.223

AC:

9245

AN:

41488

American (AMR)

AF:

0.440

AC:

6729

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1575

AN:

3468

East Asian (EAS)

AF:

0.621

AC:

3207

AN:

5164

South Asian (SAS)

AF:

0.408

AC:

1970

AN:

4826

European-Finnish (FIN)

AF:

0.589

AC:

6237

AN:

10584

Middle Eastern (MID)

AF:

0.342

AC:

100

AN:

292

European-Non Finnish (NFE)

AF:

0.484

AC:

32885

AN:

67918

Other (OTH)

AF:

0.403

AC:

848

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1855

3710

5566

7421

9276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.446

Hom.:

36158

Bravo

AF:

0.403

Asia WGS

AF:

0.432

AC:

1505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.5

(source)

DANN

Benign

0.79

PhyloP100

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over