rs2285644
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000342.4(SLC4A1):c.2561C>T(p.Pro854Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,614,206 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000342.4 missense
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC4A1 | NM_000342.4 | c.2561C>T | p.Pro854Leu | missense_variant | 19/20 | ENST00000262418.12 | NP_000333.1 | |
SLC4A1 | XM_011525129.3 | c.2471C>T | p.Pro824Leu | missense_variant | 18/19 | XP_011523431.1 | ||
SLC4A1 | XM_005257593.6 | c.2366C>T | p.Pro789Leu | missense_variant | 17/18 | XP_005257650.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC4A1 | ENST00000262418.12 | c.2561C>T | p.Pro854Leu | missense_variant | 19/20 | 1 | NM_000342.4 | ENSP00000262418.6 | ||
SLC4A1 | ENST00000399246.3 | c.1463C>T | p.Pro488Leu | missense_variant | 14/15 | 5 | ENSP00000382190.3 |
Frequencies
GnomAD3 genomes AF: 0.00346 AC: 527AN: 152220Hom.: 5 Cov.: 32
GnomAD3 exomes AF: 0.00830 AC: 2086AN: 251180Hom.: 43 AF XY: 0.00655 AC XY: 889AN XY: 135810
GnomAD4 exome AF: 0.00271 AC: 3963AN: 1461870Hom.: 76 Cov.: 33 AF XY: 0.00251 AC XY: 1828AN XY: 727242
GnomAD4 genome AF: 0.00346 AC: 527AN: 152336Hom.: 4 Cov.: 32 AF XY: 0.00361 AC XY: 269AN XY: 74480
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 29, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 13, 2020 | This variant is associated with the following publications: (PMID: 20825599, 21637597, 17137217, 24724911, 8206915, 19727826) - |
Hereditary spherocytosis type 4 Benign:2
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | 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. - |
DIEGO BLOOD GROUP ANTIGEN Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 10, 1994 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal dominant distal renal tubular acidosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | 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. - |
Hemolytic anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | 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