chr6-51911962-GAA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_138694.4(PKHD1):​c.6333-8_6333-7delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00653 in 1,606,474 control chromosomes in the GnomAD database, including 630 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 331 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 299 hom. )

Consequence

PKHD1
NM_138694.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.41
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 6-51911962-GAA-G is Benign according to our data. Variant chr6-51911962-GAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 96415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-51911962-GAA-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKHD1NM_138694.4 linkc.6333-8_6333-7delTT splice_region_variant, intron_variant Intron 38 of 66 ENST00000371117.8 NP_619639.3 P08F94-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKHD1ENST00000371117.8 linkc.6333-8_6333-7delTT splice_region_variant, intron_variant Intron 38 of 66 1 NM_138694.4 ENSP00000360158.3 P08F94-1
PKHD1ENST00000340994.4 linkc.6333-8_6333-7delTT splice_region_variant, intron_variant Intron 38 of 60 5 ENSP00000341097.4 P08F94-2

Frequencies

GnomAD3 genomes
AF:
0.0348
AC:
5284
AN:
151710
Hom.:
329
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.122
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0122
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000623
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.0244
GnomAD3 exomes
AF:
0.00901
AC:
2221
AN:
246380
Hom.:
138
AF XY:
0.00671
AC XY:
897
AN XY:
133644
show subpopulations
Gnomad AFR exome
AF:
0.128
Gnomad AMR exome
AF:
0.00538
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000233
Gnomad OTH exome
AF:
0.00385
GnomAD4 exome
AF:
0.00357
AC:
5199
AN:
1454644
Hom.:
299
AF XY:
0.00310
AC XY:
2242
AN XY:
724032
show subpopulations
Gnomad4 AFR exome
AF:
0.128
Gnomad4 AMR exome
AF:
0.00614
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000232
Gnomad4 FIN exome
AF:
0.0000192
Gnomad4 NFE exome
AF:
0.0000984
Gnomad4 OTH exome
AF:
0.00793
GnomAD4 genome
AF:
0.0349
AC:
5298
AN:
151830
Hom.:
331
Cov.:
32
AF XY:
0.0343
AC XY:
2544
AN XY:
74188
show subpopulations
Gnomad4 AFR
AF:
0.122
Gnomad4 AMR
AF:
0.0122
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.0242
Alfa
AF:
0.00134
Hom.:
0
Bravo
AF:
0.0404

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Autosomal recessive polycystic kidney disease Benign:3
Jan 23, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 29, 2017
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:3
Aug 24, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Sep 29, 2015
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Oct 31, 2016
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant summary: The PKHD1 c.6333-8_6333-7delTT variant involves the deletion of two non-conserved intronic nucleotides. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 1283/110896 control chromosomes (75 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.1271383 (1204/9470). This frequency is about 18 times the estimated maximal expected allele frequency of a pathogenic PKHD1 variant (0.0070711), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. -

not specified Benign:2
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jun 20, 2016
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Polycystic kidney disease 4 Benign:1
Jul 27, 2021
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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.

Other links and lift over

dbSNP: rs138161138; hg19: chr6-51776760; API