rs375346550
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000488.4(SERPINC1):c.1154-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000862 in 1,613,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★★).
Frequency
Consequence
NM_000488.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINC1 | NM_000488.4 | c.1154-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000367698.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINC1 | ENST00000367698.4 | c.1154-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000488.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152192Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251456Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135902
GnomAD4 exome AF: 0.0000883 AC: 129AN: 1460702Hom.: 0 Cov.: 30 AF XY: 0.000110 AC XY: 80AN XY: 726806
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152310Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74466
ClinVar
Submissions by phenotype
Hereditary antithrombin deficiency Benign:2
Likely benign, reviewed by expert panel | curation | Clingen Thrombosis Variant Curation Expert Panel, ClinGen | Jul 25, 2023 | The NM_000488.4(SERPINC1):c.1154-5T>C variant is an intronic change that has a frequency of 0.03% in South Asians with 11 alleles (gnomAD v2.1.1). No splicing disruption prediction is noted per SpliceAI and varSEAK, but the nucleotide may be moderately conserved. In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BS1, BP4. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 22, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at