chr6-116628384-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001010892.3(RSPH4A):c.1662+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,584,112 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001010892.3 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.1662+15C>T | intron_variant | Intron 3 of 5 | 1 | NM_001010892.3 | ENSP00000229554.5 | |||
RSPH4A | ENST00000368581.8 | c.1662+15C>T | intron_variant | Intron 3 of 4 | 1 | ENSP00000357570.4 | ||||
RSPH4A | ENST00000368580.4 | c.922-1183C>T | intron_variant | Intron 2 of 4 | 5 | ENSP00000357569.4 |
Frequencies
GnomAD3 genomes AF: 0.00135 AC: 206AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00162 AC: 396AN: 244194Hom.: 4 AF XY: 0.00163 AC XY: 216AN XY: 132660
GnomAD4 exome AF: 0.00167 AC: 2395AN: 1431890Hom.: 8 Cov.: 25 AF XY: 0.00172 AC XY: 1226AN XY: 714268
GnomAD4 genome AF: 0.00135 AC: 206AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.00130 AC XY: 97AN XY: 74422
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 11 Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:1
c.1662+15C>T in intron 3 of RSPH4A: This variant is not expected to have clinica l significance because it is not located within the splice consensus sequence. I t has been identified in 0.2% (164/65466) of European chromosomes, including 2 h omozygotes, by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs183372450). -
Primary ciliary dyskinesia Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at