15-57970983-G-C

Variant names:

• chr15-57970983-G-C
• rs1837853
• NM_003888.4:c.799-5156C>G

Variant summary

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

The NM_003888.4(ALDH1A2):​c.799-5156C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,234 control chromosomes in the GnomAD database, including 61,464 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 0.89 (61464 hom., cov: 32)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 2 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.799-5156C>G		intron_variant	Intron 7 of 12	ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.736-5156C>G		intron_variant	Intron 8 of 13		NP_001193826.1
ALDH1A2	NM_170696.3	c.685-5156C>G		intron_variant	Intron 6 of 11		NP_733797.1
ALDH1A2	NM_170697.3	c.511-5156C>G		intron_variant	Intron 5 of 10		NP_733798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.799-5156C>G		intron_variant	Intron 7 of 12	1	NM_003888.4	ENSP00000249750.4

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135369 AN: 152116 Hom.: 61432 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.890 AC: 135455 AN: 152234 Hom.: 61464 Cov.: 32 AF XY: 0.893 AC XY: 66467 AN XY: 74434

African (AFR) AF: 0.689 AC: 28595 AN: 41502

American (AMR) AF: 0.953 AC: 14572 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 3280 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5175 AN: 5176

South Asian (SAS) AF: 0.984 AC: 4743 AN: 4822

European-Finnish (FIN) AF: 0.969 AC: 10288 AN: 10612

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.966 AC: 65704 AN: 68032

Other (OTH) AF: 0.919 AC: 1945 AN: 2116

Alfa AF: 0.921 Hom.: 8108

Bravo AF: 0.878

Asia WGS AF: 0.979 AC: 3406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-0.40
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: rs1837853; hg19: chr15-58263181;