rs13182402

Positions:

• chr5-126582456-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001182.5(ALDH7A1):​c.517+395T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,136 control chromosomes in the GnomAD database, including 1,956 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 0.14 (1956 hom., cov: 32)
• Consequence: ALDH7A1 NM_001182.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

Genes affected

ALDH7A1 (HGNC:877): (aldehyde dehydrogenase 7 family member A1) The protein encoded by this gene is a member of subfamily 7 in the aldehyde dehydrogenase gene family. These enzymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular member has homology to a previously described protein from the green garden pea, the 26g pea turgor protein. It is also involved in lysine catabolism that is known to occur in the mitochondrial matrix. Recent reports show that this protein is found both in the cytosol and the mitochondria, and the two forms likely arise from the use of alternative translation initiation sites. An additional variant encoding a different isoform has also been found for this gene. Mutations in this gene are associated with pyridoxine-dependent epilepsy. Several related pseudogenes have also been identified. [provided by RefSeq, Jan 2011]

ALDH7A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH7A1	NM_001182.5	c.517+395T>C		intron_variant		ENST00000409134.8	NP_001173.2
ALDH7A1	NM_001201377.2	c.433+395T>C		intron_variant			NP_001188306.1
ALDH7A1	NM_001202404.2	c.517+395T>C		intron_variant			NP_001189333.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000409134.8	c.517+395T>C		intron_variant		1	NM_001182.5	ENSP00000387123.3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21580 AN: 152018 Hom.: 1953 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21609 AN: 152136 Hom.: 1956 Cov.: 32 AF XY: 0.140 AC XY: 10429 AN XY: 74374

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0560

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0756

Gnomad4 NFE AF: 0.0998

Gnomad4 OTH AF: 0.133

Alfa AF: 0.108 Hom.: 1909

Bravo AF: 0.148

Asia WGS AF: 0.153 AC: 530 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13182402; hg19: chr5-125918148;