rs13182402

Variant names:

• chr5-126582456-A-G
• rs13182402
• NM_001182.5:c.517+395T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 publications found

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 Gene-Disease associations (from GenCC):

• pyridoxine-dependent epilepsy

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina, ClinGen
• pyridoxine-dependent epilepsy caused by ALDH7A1 mutant

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001182.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH7A1	NM_001182.5	MANE Select	c.517+395T>C		intron	N/A	NP_001173.2	P49419-1
	ALDH7A1	NM_001201377.2		c.433+395T>C		intron	N/A	NP_001188306.1	P49419-2
	ALDH7A1	NM_001202404.2		c.517+395T>C		intron	N/A	NP_001189333.2	P49419-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH7A1	ENST00000409134.8	TSL:1 MANE Select	c.517+395T>C		intron	N/A	ENSP00000387123.3	P49419-1
	ALDH7A1	ENST00000636879.1	TSL:5	c.518-307T>C		intron	N/A	ENSP00000490811.1	A0A1B0GW77
	ALDH7A1	ENST00000939100.1		c.517+395T>C		intron	N/A	ENSP00000609159.1

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

African (AFR) AF: 0.253 AC: 10514 AN: 41510

American (AMR) AF: 0.108 AC: 1649 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3470

East Asian (EAS) AF: 0.0560 AC: 290 AN: 5178

South Asian (SAS) AF: 0.157 AC: 757 AN: 4822

European-Finnish (FIN) AF: 0.0756 AC: 800 AN: 10586

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0998 AC: 6785 AN: 68008

Other (OTH) AF: 0.133 AC: 281 AN: 2110

Alfa AF: 0.113 Hom.: 5040

Bravo AF: 0.148

Asia WGS AF: 0.153 AC: 530 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13182402; hg19: chr5-125918148;