rs17624021
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002775.5(HTRA1):c.753C>T(p.Ile251Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 1,613,730 control chromosomes in the GnomAD database, including 2,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_002775.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HTRA1 | ENST00000368984.8 | c.753C>T | p.Ile251Ile | synonymous_variant | Exon 3 of 9 | 1 | NM_002775.5 | ENSP00000357980.3 | ||
HTRA1 | ENST00000648167.1 | c.435C>T | p.Ile145Ile | synonymous_variant | Exon 3 of 9 | ENSP00000498033.1 |
Frequencies
GnomAD3 genomes AF: 0.0408 AC: 6208AN: 152068Hom.: 141 Cov.: 33
GnomAD3 exomes AF: 0.0412 AC: 10358AN: 251438Hom.: 276 AF XY: 0.0423 AC XY: 5750AN XY: 135900
GnomAD4 exome AF: 0.0506 AC: 74011AN: 1461544Hom.: 2115 Cov.: 32 AF XY: 0.0508 AC XY: 36901AN XY: 727082
GnomAD4 genome AF: 0.0408 AC: 6211AN: 152186Hom.: 141 Cov.: 33 AF XY: 0.0415 AC XY: 3086AN XY: 74398
ClinVar
Submissions by phenotype
not provided Benign:5Other:1
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not specified Benign:1
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Macular degeneration Benign: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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at