ENST00000558231.5:c.30+34978G>C

Variant names:

• chr15-58244196-C-G
• rs8034444
• ENST00000558231.5:c.30+34978G>C

Variant summary

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

The ENST00000558231.5(ALDH1A2):​c.30+34978G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,104 control chromosomes in the GnomAD database, including 21,066 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 0.52 (21066 hom., cov: 32)
• Consequence: ALDH1A2 ENST00000558231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 0 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)

LOC124903499 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903499	XR_007064653.1	n.177-57C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000558231.5	c.30+34978G>C		intron_variant	Intron 1 of 12	2		ENSP00000453600.1
ALDH1A2	ENST00000558239.5	c.-172+175775G>C		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000558073.5	n.265+1939G>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78653 AN: 151988 Hom.: 21067 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.517 AC: 78685 AN: 152104 Hom.: 21066 Cov.: 32 AF XY: 0.513 AC XY: 38179 AN XY: 74368

African (AFR) AF: 0.424 AC: 17576 AN: 41492

American (AMR) AF: 0.423 AC: 6470 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1919 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1927 AN: 5168

South Asian (SAS) AF: 0.442 AC: 2131 AN: 4820

European-Finnish (FIN) AF: 0.584 AC: 6169 AN: 10572

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40664 AN: 67980

Other (OTH) AF: 0.506 AC: 1067 AN: 2110

Alfa AF: 0.435 Hom.: 1258

Bravo AF: 0.504

Asia WGS AF: 0.389 AC: 1354 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	1.8
DANN	Benign	0.28
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8034444; hg19: chr15-58536395;