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
Consequence
NM_138694.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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PKHD1 | ENST00000371117.8 | c.6333-8_6333-7delTT | splice_region_variant, intron_variant | Intron 38 of 66 | 1 | NM_138694.4 | ENSP00000360158.3 | |||
PKHD1 | ENST00000340994.4 | c.6333-8_6333-7delTT | splice_region_variant, intron_variant | Intron 38 of 60 | 5 | ENSP00000341097.4 |
Frequencies
GnomAD3 genomes AF: 0.0348 AC: 5284AN: 151710Hom.: 329 Cov.: 32
GnomAD3 exomes AF: 0.00901 AC: 2221AN: 246380Hom.: 138 AF XY: 0.00671 AC XY: 897AN XY: 133644
GnomAD4 exome AF: 0.00357 AC: 5199AN: 1454644Hom.: 299 AF XY: 0.00310 AC XY: 2242AN XY: 724032
GnomAD4 genome AF: 0.0349 AC: 5298AN: 151830Hom.: 331 Cov.: 32 AF XY: 0.0343 AC XY: 2544AN XY: 74188
ClinVar
Submissions by phenotype
Autosomal recessive polycystic kidney disease Benign:3
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not provided Benign:3
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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
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Polycystic kidney disease 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at