rs4471613

Variant names:

• chr15-58259495-G-A
• rs4471613
• ENST00000558231.5:c.30+19679C>T

Variant summary

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

The ENST00000558231.5(ALDH1A2):​c.30+19679C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 151,914 control chromosomes in the GnomAD database, including 176 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 0.044 (176 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0598 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	ENST00000558231.5	c.30+19679C>T		intron_variant	Intron 1 of 12	2		ENSP00000453600.1
ALDH1A2	ENST00000558239.5	c.-172+160476C>T		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000558073.5	n.98-13193C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0440 AC: 6672 AN: 151796 Hom.: 176 Cov.: 31

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.0527

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

GnomAD4 genome AF: 0.0439 AC: 6667 AN: 151914 Hom.: 176 Cov.: 31 AF XY: 0.0432 AC XY: 3207 AN XY: 74238

African (AFR) AF: 0.0208 AC: 863 AN: 41408

American (AMR) AF: 0.0430 AC: 656 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3464

East Asian (EAS) AF: 0.0655 AC: 339 AN: 5174

South Asian (SAS) AF: 0.0334 AC: 160 AN: 4784

European-Finnish (FIN) AF: 0.0465 AC: 490 AN: 10536

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0528 AC: 3586 AN: 67968

Other (OTH) AF: 0.0521 AC: 110 AN: 2110

Alfa AF: 0.0454 Hom.: 27

Bravo AF: 0.0417

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.44
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4471613; hg19: chr15-58551694;