15-57979546-A-G

Variant names:

• chr15-57979546-A-G
• rs2012147
• NM_003888.4:c.798+13159T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003888.4(ALDH1A2):​c.798+13159T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,154 control chromosomes in the GnomAD database, including 57,938 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 0.86 (57938 hom., cov: 33)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 3 publications found

Genes affected

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ALDH1A2 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

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

LOC100418848 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.798+13159T>C		intron_variant	Intron 7 of 12	ENST00000249750.9	NP_003879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.798+13159T>C		intron_variant	Intron 7 of 12	1	NM_003888.4	ENSP00000249750.4

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130407 AN: 152036 Hom.: 57921 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.857 AC: 130467 AN: 152154 Hom.: 57938 Cov.: 33 AF XY: 0.861 AC XY: 64085 AN XY: 74388

African (AFR) AF: 0.597 AC: 24754 AN: 41436

American (AMR) AF: 0.921 AC: 14085 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3251 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5149 AN: 5154

South Asian (SAS) AF: 0.973 AC: 4700 AN: 4828

European-Finnish (FIN) AF: 0.968 AC: 10281 AN: 10620

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.959 AC: 65204 AN: 68024

Other (OTH) AF: 0.895 AC: 1893 AN: 2116

Alfa AF: 0.838 Hom.: 3224

Bravo AF: 0.842

Asia WGS AF: 0.950 AC: 3306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		-1.9
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: rs2012147; hg19: chr15-58271744;