chr12-111799896-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_000690.4(ALDH2):c.1249-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000684 in 1,612,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00070 ( 0 hom. )
Consequence
ALDH2
NM_000690.4 splice_polypyrimidine_tract, intron
NM_000690.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001260
2
Clinical Significance
Conservation
PhyloP100: 0.129
Genes affected
ALDH2 (HGNC:404): (aldehyde dehydrogenase 2 family member) This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Nov 2016]
MIR6761 (HGNC:49949): (microRNA 6761) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 12-111799896-C-T is Benign according to our data. Variant chr12-111799896-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 728511.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH2 | NM_000690.4 | c.1249-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000261733.7 | |||
MIR6761 | NR_106819.1 | n.63C>T | non_coding_transcript_exon_variant | 1/1 | |||
ALDH2 | NM_001204889.2 | c.1108-10C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH2 | ENST00000261733.7 | c.1249-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000690.4 | P1 | |||
MIR6761 | ENST00000617899.1 | n.63C>T | mature_miRNA_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.000552 AC: 84AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000485 AC: 121AN: 249720Hom.: 0 AF XY: 0.000452 AC XY: 61AN XY: 134948
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GnomAD4 exome AF: 0.000697 AC: 1018AN: 1459770Hom.: 0 Cov.: 30 AF XY: 0.000701 AC XY: 509AN XY: 726024
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GnomAD4 genome AF: 0.000551 AC: 84AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42AN XY: 74490
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 21, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at