rs4775041

Variant names:

• chr15-58382496-G-C
• rs4775041
• ENST00000558239.5:c.-172+37475C>G

Variant summary

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

The ENST00000558239.5(ALDH1A2):​c.-172+37475C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,182 control chromosomes in the GnomAD database, including 4,881 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 0.24 (4881 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 82 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000558239.5	c.-172+37475C>G		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000560863.5	n.415+37475C>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36210 AN: 152064 Hom.: 4878 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.238 AC: 36224 AN: 152182 Hom.: 4881 Cov.: 32 AF XY: 0.239 AC XY: 17752 AN XY: 74400

African (AFR) AF: 0.128 AC: 5310 AN: 41532

American (AMR) AF: 0.225 AC: 3445 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 869 AN: 3468

East Asian (EAS) AF: 0.191 AC: 988 AN: 5166

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4818

European-Finnish (FIN) AF: 0.348 AC: 3684 AN: 10600

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20095 AN: 67988

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.275 Hom.: 3392

Bravo AF: 0.222

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.66
PhyloP100		-0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4775041; hg19: chr15-58674695;