chr6-51831038-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138694.4(PKHD1):c.8174-49G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 1,441,370 control chromosomes in the GnomAD database, including 2,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 240 hom., cov: 32)

Exomes 𝑓: 0.051 ( 1960 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.774

Publications

4 publications found

Variant links:

Genes affected

PKHD1 (HGNC:9016): (PKHD1 ciliary IPT domain containing fibrocystin/polyductin) The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [provided by RefSeq, Jul 2008]

PKHD1 Gene-Disease associations (from GenCC):

autosomal recessive polycystic kidney disease
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Orphanet
polycystic kidney disease 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Genomics England PanelApp
Caroli disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PKHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-51831038-C-G is Benign according to our data. Variant chr6-51831038-C-G is described in ClinVar as Benign. ClinVar VariationId is 262420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.8174-49G>C		intron_variant	Intron 51 of 66	ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8 link	c.8174-49G>C		intron_variant	Intron 51 of 66	1	NM_138694.4	ENSP00000360158.3
PKHD1	ENST00000340994.4 link	c.8174-49G>C		intron_variant	Intron 51 of 60	5		ENSP00000341097.4

Frequencies

GnomAD3 genomes

AF:

0.0545

AC:

8296

AN:

152092

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.0524

Gnomad SAS

AF:

0.0726

Gnomad FIN

AF:

0.0571

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0524

Gnomad OTH

AF:

0.0455

GnomAD2 exomes

AF:

0.0532

AC:

11776

AN:

221222

AF XY:

0.0536

show subpopulations

Gnomad AFR exome

AF:

0.0666

Gnomad AMR exome

AF:

0.0402

Gnomad ASJ exome

AF:

0.0356

Gnomad EAS exome

AF:

0.0344

Gnomad FIN exome

AF:

0.0585

Gnomad NFE exome

AF:

0.0519

Gnomad OTH exome

AF:

0.0606

GnomAD4 exome

AF:

0.0513

AC:

66114

AN:

1289160

Hom.:

1960

Cov.:

AF XY:

0.0522

AC XY:

33854

AN XY:

649146

show subpopulations

African (AFR)

AF:

0.0667

AC:

1979

AN:

29662

American (AMR)

AF:

0.0401

AC:

1693

AN:

42208

Ashkenazi Jewish (ASJ)

AF:

0.0379

AC:

941

AN:

24806

East Asian (EAS)

AF:

0.0849

AC:

3217

AN:

37906

South Asian (SAS)

AF:

0.0733

AC:

5933

AN:

80954

European-Finnish (FIN)

AF:

0.0568

AC:

2955

AN:

52042

Middle Eastern (MID)

AF:

0.0340

AC:

164

AN:

4828

European-Non Finnish (NFE)

AF:

0.0484

AC:

46555

AN:

962460

Other (OTH)

AF:

0.0493

AC:

2677

AN:

54294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

3052

6105

9157

12210

15262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1608

3216

4824

6432

8040

<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:

0.0547

AC:

8327

AN:

152210

Hom.:

240

Cov.:

AF XY:

0.0548

AC XY:

4079

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0656

AC:

2726

AN:

41534

American (AMR)

AF:

0.0370

AC:

566

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

121

AN:

3470

East Asian (EAS)

AF:

0.0530

AC:

274

AN:

5174

South Asian (SAS)

AF:

0.0725

AC:

349

AN:

4816

European-Finnish (FIN)

AF:

0.0571

AC:

605

AN:

10596

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0524

AC:

3566

AN:

68020

Other (OTH)

AF:

0.0483

AC:

102

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

395

789

1184

1578

1973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0571

Hom.:

Bravo

AF:

0.0522

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Autosomal recessive polycystic kidney disease

Benign:1

Apr 13, 2018

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

(source)

DANN

Benign

0.66

PhyloP100

-0.77

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over