rs1802603

Variant names:

• chr15-100916579-G-A
• rs1802603
• NM_000693.4:c.*1806G>A

Variant summary

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

The NM_000693.4(ALDH1A3):​c.*1806G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,246 control chromosomes in the GnomAD database, including 1,763 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 0.10 (1763 hom., cov: 33)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: ALDH1A3 NM_000693.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 7 publications found

Genes affected

ALDH1A3 (HGNC:409): (aldehyde dehydrogenase 1 family member A3) This gene encodes an aldehyde dehydrogenase enzyme that uses retinal as a substrate. Mutations in this gene have been associated with microphthalmia, isolated 8, and expression changes have also been detected in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ALDH1A3-AS1 (HGNC:55416): (ALDH1A3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	NM_000693.4	MANE Select	c.*1806G>A		3_prime_UTR	Exon 13 of 13	NP_000684.2
	ALDH1A3	NM_001293815.2		c.*1806G>A		3_prime_UTR	Exon 10 of 10	NP_001280744.1
	ALDH1A3-AS1	NR_135827.1		n.480+2225C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.*1806G>A		3_prime_UTR	Exon 13 of 13	ENSP00000332256.5
	ALDH1A3	ENST00000346623.6	TSL:1	c.*1806G>A		3_prime_UTR	Exon 10 of 10	ENSP00000343294.6
	ALDH1A3-AS1	ENST00000560068.2	TSL:1	n.491-599C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15927 AN: 152096 Hom.: 1754 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0251

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.0625 AC: 2 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.0417 AC XY: 1 AN XY: 24

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0625 AC: 2 AN: 32

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.105 AC: 15966 AN: 152214 Hom.: 1763 Cov.: 33 AF XY: 0.105 AC XY: 7848 AN XY: 74432

African (AFR) AF: 0.281 AC: 11646 AN: 41490

American (AMR) AF: 0.0623 AC: 953 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3470

East Asian (EAS) AF: 0.0684 AC: 354 AN: 5178

South Asian (SAS) AF: 0.0542 AC: 262 AN: 4832

European-Finnish (FIN) AF: 0.0535 AC: 567 AN: 10604

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0252 AC: 1711 AN: 68022

Other (OTH) AF: 0.0957 AC: 202 AN: 2110

Alfa AF: 0.0617 Hom.: 1471

Bravo AF: 0.112

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.52
PhyloP100		0.47
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: rs1802603; hg19: chr15-101456784;