rs7192711
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001009944.3(PKD1):c.10822-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,570,898 control chromosomes in the GnomAD database, including 483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001009944.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.10822-14C>T | intron_variant | Intron 36 of 45 | ENST00000262304.9 | NP_001009944.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0320 AC: 4864AN: 152146Hom.: 274 Cov.: 33
GnomAD3 exomes AF: 0.00815 AC: 1467AN: 179918Hom.: 69 AF XY: 0.00640 AC XY: 626AN XY: 97758
GnomAD4 exome AF: 0.00343 AC: 4865AN: 1418634Hom.: 208 Cov.: 32 AF XY: 0.00300 AC XY: 2107AN XY: 702524
GnomAD4 genome AF: 0.0321 AC: 4885AN: 152264Hom.: 275 Cov.: 33 AF XY: 0.0316 AC XY: 2356AN XY: 74460
ClinVar
Submissions by phenotype
not specified Benign:1
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Polycystic kidney disease, adult type Benign:1
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Polycystic kidney disease Benign:1
The PKD1 c.10822-14C>T variant was identified in 3 of 460 proband chromosomes (frequency: 0.007) from American individuals or families with ADPKD (Rossetti 2012). The variant was also identified in dbSNP (ID: rs7192711) as “With Benign allele”, the ADPKD Mutation Database (classification likely neutral), the 1000 Genomes Project in 165 of 5015 chromosomes (frequency: 0.03), HAPMAP-YRI in 26 of 226 chromosomes (frequency: 0.115), HAPMAP-ASW in 12 of 98 chromosomes (frequency: 0.122), HAPMAP-LWK in 22 of 189 chromosomes (frequency: 0.122), the NHLBI GO Exome Sequencing Project in 8 of 8552 European American alleles (frequency: 0.0009) and in 453 of 4362 African American alleles (frequency: 0.1), and in the Exome Aggregation Consortium database (August 8, 2016) in 531 of 33314 chromosomes (29 homozgyous) (frequency: 0.02) in the following populations: African in 466 (29 homozygotes) of 3264 chromosomes (frequency: 0.1), Latino in 31 of 2608 chromosomes (frequency: 0.01), Other in 2 of 280 chromosomes (frequency: 0.007), European (Non-Finnish) in 110 of 64720 chromosomes (frequency: 0.002), and South Asian in 1 of 9322 chromosomes (frequency: 0.0001), but was not seen in East Asian and Finnish and populations. The variant was also identified in Clinvitae (classification benign), ClinVar (classification benign, submitter Prevention Genetics), but was not in GeneInsight-COGR, PKD1-LOVD, and PKD1-LOVD 3.0. The variant was identified by our laboratory in 1 individual with ADPKD, co-occurring with a pathogenic PKD1 variant (c.12178C>T, p.Gln4060X), increasing the likelihood that the variant does not have clinical significance. The c.10822-14C>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. In addition, five of five in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a greater than 10% difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at