rs28525570
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_003126.4(SPTA1):c.6531-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,602,240 control chromosomes in the GnomAD database, including 60,252 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_003126.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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SPTA1 | NM_003126.4 | c.6531-12C>T | intron_variant | Intron 45 of 51 | ENST00000643759.2 | NP_003117.2 | ||
SPTA1 | XM_011509916.3 | c.6531-12C>T | intron_variant | Intron 46 of 52 | XP_011508218.1 | |||
SPTA1 | XM_011509917.4 | c.6531-480C>T | intron_variant | Intron 45 of 50 | XP_011508219.1 | |||
SPTA1 | XM_047428883.1 | c.6210-12C>T | intron_variant | Intron 45 of 51 | XP_047284839.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.254 AC: 38595AN: 151962Hom.: 5120 Cov.: 32
GnomAD3 exomes AF: 0.254 AC: 63402AN: 249186Hom.: 8413 AF XY: 0.259 AC XY: 35021AN XY: 135198
GnomAD4 exome AF: 0.271 AC: 393274AN: 1450160Hom.: 55131 Cov.: 32 AF XY: 0.272 AC XY: 196331AN XY: 721926
GnomAD4 genome AF: 0.254 AC: 38604AN: 152080Hom.: 5121 Cov.: 32 AF XY: 0.255 AC XY: 18981AN XY: 74334
ClinVar
Submissions by phenotype
not provided Pathogenic:1Benign:2
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SPTA1: BS1, BS2 -
Commonly referred to as the AlphaLELY allele, this variant is a low expression allele that results in partial skipping of exon 46 and expression of hereditary elliptocytosis when in trans with a pathogenic SPTA1 variant (Wilmotte et al., 1999); This variant has been reported multiple times in association with hereditary elliptocytosis when present in trans with a pathogenic SPTA1 variant (Russo et al., 2018; Aggarwal et al., 2020; Suzuki et al., 2021) This variant is associated with the following publications: (PMID: 10192450, 29396846, 31602632, 32287101, 29484404, 30298500, 32581362) -
not specified Uncertain:1Benign:1
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Hemolytic anemia Pathogenic:1
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Elliptocytosis 2 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Hereditary spherocytosis type 3 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Pyropoikilocytosis, hereditary Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at