5-126551993-C-T

Variant names:

• chr5-126551993-C-T
• rs2306617
• NM_001182.5:c.1317+28G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001182.5(ALDH7A1):​c.1317+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,488,570 control chromosomes in the GnomAD database, including 387,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38538 hom., cov: 32)
  • Exomes 𝑓: 0.72 (348644 hom.)
• Consequence: ALDH7A1 NM_001182.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.968

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 5-126551993-C-T is Benign according to our data. Variant chr5-126551993-C-T is described in ClinVar as [Benign]. Clinvar id is 1188913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH7A1	NM_001182.5	c.1317+28G>A		intron_variant	Intron 14 of 17	ENST00000409134.8	NP_001173.2
ALDH7A1	NM_001201377.2	c.1233+28G>A		intron_variant	Intron 14 of 17		NP_001188306.1
ALDH7A1	NM_001202404.2	c.1125+28G>A		intron_variant	Intron 12 of 15		NP_001189333.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000409134.8	c.1317+28G>A		intron_variant	Intron 14 of 17	1	NM_001182.5	ENSP00000387123.3

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107840 AN: 151950 Hom.: 38503 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.698

GnomAD3 exomes AF: 0.714 AC: 178740 AN: 250284 Hom.: 64295 AF XY: 0.707 AC XY: 95622 AN XY: 135340

Gnomad AFR exome AF: 0.682

Gnomad AMR exome AF: 0.823

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.745

Gnomad SAS exome AF: 0.616

Gnomad FIN exome AF: 0.683

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.720 AC: 962595 AN: 1336500 Hom.: 348644 Cov.: 19 AF XY: 0.716 AC XY: 481169 AN XY: 672036

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.817

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.728

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.710 AC: 107920 AN: 152070 Hom.: 38538 Cov.: 32 AF XY: 0.707 AC XY: 52567 AN XY: 74340

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.703

Alfa AF: 0.718 Hom.: 69225

Bravo AF: 0.720

Asia WGS AF: 0.681 AC: 2370 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 87% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 81. Only high quality variants are reported. -

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pyridoxine-dependent epilepsy Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2306617; hg19: chr5-125887685;