rs1205339301

Variant names:

• chr5-126595266-C-T
• rs1205339301
• ENST00000636808.1:n.-68G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The ENST00000636808.1(ALDH7A1):​n.-68G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000602 in 996,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000070 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: ALDH7A1 ENST00000636808.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 0 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: Illumina, Orphanet, ClinGen
• pyridoxine-dependent epilepsy caused by ALDH7A1 mutant

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636808.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH7A1	NM_001182.5	MANE Select	c.-68G>A		upstream_gene	N/A	NP_001173.2
	ALDH7A1	NM_001201377.2		c.-152G>A		upstream_gene	N/A	NP_001188306.1
	ALDH7A1	NM_001202404.2		c.-68G>A		upstream_gene	N/A	NP_001189333.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH7A1	ENST00000636808.1	TSL:5	n.-68G>A		non_coding_transcript_exon	Exon 1 of 18	ENSP00000490833.1
	ALDH7A1	ENST00000637206.1	TSL:5	c.-68G>A		5_prime_UTR	Exon 1 of 16	ENSP00000489895.1
	ALDH7A1	ENST00000553117.5	TSL:2	c.-68G>A		5_prime_UTR	Exon 1 of 16	ENSP00000448593.1

Frequencies

GnomAD3 genomes AF: 0.00000705 AC: 1 AN: 141898 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000244

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000416 AC: 6 AN: 144086 AF XY: 0.0000385

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000563

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000585 AC: 5 AN: 854994 Hom.: 0 Cov.: 34 AF XY: 0.00000697 AC XY: 3 AN XY: 430280

African (AFR) AF: 0.00 AC: 0 AN: 21780

American (AMR) AF: 0.00 AC: 0 AN: 29396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15720

East Asian (EAS) AF: 0.000348 AC: 5 AN: 14358

South Asian (SAS) AF: 0.00 AC: 0 AN: 69960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3888

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 634868

Other (OTH) AF: 0.00 AC: 0 AN: 34306

GnomAD4 genome AF: 0.00000705 AC: 1 AN: 141898 Hom.: 0 Cov.: 30 AF XY: 0.0000145 AC XY: 1 AN XY: 68836

African (AFR) AF: 0.00 AC: 0 AN: 39750

American (AMR) AF: 0.00 AC: 0 AN: 14416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3302

East Asian (EAS) AF: 0.000244 AC: 1 AN: 4106

South Asian (SAS) AF: 0.00 AC: 0 AN: 3884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64356

Other (OTH) AF: 0.00 AC: 0 AN: 1992

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		2.2
PromoterAI		0.029	Neutral

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: rs1205339301; hg19: chr5-125930958;