15-57960908-T-C

Variant names:

• chr15-57960908-T-C
• rs3784262
• NM_003888.4:c.1410-64A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003888.4(ALDH1A2):​c.1410-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,463,828 control chromosomes in the GnomAD database, including 133,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11132 hom., cov: 33)
  • Exomes 𝑓: 0.42 (122302 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0730
• Publications: 26 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: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-57960908-T-C is Benign according to our data. Variant chr15-57960908-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003888.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	NM_003888.4	MANE Select	c.1410-64A>G		intron	N/A	NP_003879.2
	ALDH1A2	NM_001206897.2		c.1347-64A>G		intron	N/A	NP_001193826.1	O94788-3
	ALDH1A2	NM_170696.3		c.1296-64A>G		intron	N/A	NP_733797.1	O94788-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	ENST00000249750.9	TSL:1 MANE Select	c.1410-64A>G		intron	N/A	ENSP00000249750.4	O94788-1
	ALDH1A2	ENST00000347587.7	TSL:1	c.1296-64A>G		intron	N/A	ENSP00000309623.3	O94788-2
	ALDH1A2	ENST00000559517.5	TSL:1	c.1122-64A>G		intron	N/A	ENSP00000453408.1	O94788-4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56231 AN: 152006 Hom.: 11131 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.422 AC: 553104 AN: 1311704 Hom.: 122302 Cov.: 19 AF XY: 0.415 AC XY: 273269 AN XY: 658638

African (AFR) AF: 0.275 AC: 8129 AN: 29610

American (AMR) AF: 0.244 AC: 9798 AN: 40232

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 8603 AN: 24430

East Asian (EAS) AF: 0.195 AC: 7565 AN: 38890

South Asian (SAS) AF: 0.194 AC: 15434 AN: 79478

European-Finnish (FIN) AF: 0.465 AC: 24441 AN: 52552

Middle Eastern (MID) AF: 0.306 AC: 1673 AN: 5462

European-Non Finnish (NFE) AF: 0.462 AC: 455886 AN: 985914

Other (OTH) AF: 0.391 AC: 21575 AN: 55136

GnomAD4 genome AF: 0.370 AC: 56246 AN: 152124 Hom.: 11132 Cov.: 33 AF XY: 0.365 AC XY: 27172 AN XY: 74350

African (AFR) AF: 0.271 AC: 11233 AN: 41498

American (AMR) AF: 0.299 AC: 4572 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1015 AN: 5174

South Asian (SAS) AF: 0.171 AC: 826 AN: 4818

European-Finnish (FIN) AF: 0.474 AC: 5004 AN: 10558

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31119 AN: 67988

Other (OTH) AF: 0.356 AC: 754 AN: 2116

Alfa AF: 0.416 Hom.: 24885

Bravo AF: 0.355

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.47
PhyloP100		-0.073
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: rs3784262; hg19: chr15-58253106;