rs75705742
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_003748.4(ALDH4A1):c.62+5317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 505,514 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.012 ( 30 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 9 hom. )
Consequence
ALDH4A1
NM_003748.4 intron
NM_003748.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.59
Genes affected
ALDH4A1 (HGNC:406): (aldehyde dehydrogenase 4 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]
MIR1290 (HGNC:35283): (microRNA 1290) 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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1887/152308) while in subpopulation AFR AF= 0.0426 (1772/41560). AF 95% confidence interval is 0.041. There are 30 homozygotes in gnomad4. There are 923 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 30 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH4A1 | NM_003748.4 | c.62+5317C>T | intron_variant | ENST00000375341.8 | |||
MIR1290 | NR_031622.1 | n.4C>T | non_coding_transcript_exon_variant | 1/1 | |||
ALDH4A1 | NM_001319218.2 | c.62+5317C>T | intron_variant | ||||
ALDH4A1 | NM_170726.3 | c.62+5317C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH4A1 | ENST00000375341.8 | c.62+5317C>T | intron_variant | 1 | NM_003748.4 | P1 | |||
MIR1290 | ENST00000408735.1 | n.4C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0124 AC: 1888AN: 152190Hom.: 30 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1888
AN:
152190
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00332 AC: 638AN: 192218Hom.: 16 AF XY: 0.00253 AC XY: 264AN XY: 104204
GnomAD3 exomes
AF:
AC:
638
AN:
192218
Hom.:
AF XY:
AC XY:
264
AN XY:
104204
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00165 AC: 584AN: 353206Hom.: 9 Cov.: 0 AF XY: 0.00127 AC XY: 255AN XY: 200848
GnomAD4 exome
AF:
AC:
584
AN:
353206
Hom.:
Cov.:
0
AF XY:
AC XY:
255
AN XY:
200848
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0124 AC: 1887AN: 152308Hom.: 30 Cov.: 32 AF XY: 0.0124 AC XY: 923AN XY: 74476
GnomAD4 genome
?
AF:
AC:
1887
AN:
152308
Hom.:
Cov.:
32
AF XY:
AC XY:
923
AN XY:
74476
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
3
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at