chr2-203956771-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_012092.4(ICOS):c.501+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,553,720 control chromosomes in the GnomAD database, including 19,510 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_012092.4 splice_region, 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 |
---|---|---|---|---|---|---|---|---|
ICOS | NM_012092.4 | c.501+6C>T | splice_region_variant, intron_variant | Intron 3 of 4 | ENST00000316386.11 | NP_036224.1 | ||
ICOS | XM_047444022.1 | c.504+6C>T | splice_region_variant, intron_variant | Intron 3 of 4 | XP_047299978.1 | |||
ICOS | XR_007073112.1 | n.553+6C>T | splice_region_variant, intron_variant | Intron 3 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ICOS | ENST00000316386.11 | c.501+6C>T | splice_region_variant, intron_variant | Intron 3 of 4 | 1 | NM_012092.4 | ENSP00000319476.6 | |||
ICOS | ENST00000435193.1 | c.501+6C>T | splice_region_variant, intron_variant | Intron 3 of 3 | 1 | ENSP00000415951.1 |
Frequencies
GnomAD3 genomes AF: 0.137 AC: 20769AN: 151918Hom.: 1506 Cov.: 32
GnomAD3 exomes AF: 0.157 AC: 39363AN: 250604Hom.: 3462 AF XY: 0.163 AC XY: 22082AN XY: 135426
GnomAD4 exome AF: 0.156 AC: 217971AN: 1401684Hom.: 17998 Cov.: 24 AF XY: 0.159 AC XY: 111277AN XY: 701004
GnomAD4 genome AF: 0.137 AC: 20783AN: 152036Hom.: 1512 Cov.: 32 AF XY: 0.139 AC XY: 10362AN XY: 74322
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 1 Benign:3
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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. -
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not specified Benign:2
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -
not provided Benign:2
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at