15-100910705-C-T

Variant names:

• chr15-100910705-C-T
• rs3803428
• NM_000693.4:c.1466+2223C>T

Variant summary

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

The NM_000693.4(ALDH1A3):​c.1466+2223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,046 control chromosomes in the GnomAD database, including 22,091 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 0.53 (22091 hom., cov: 32)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.1466+2223C>T		intron_variant	Intron 12 of 12	ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.1145+2223C>T		intron_variant	Intron 9 of 9		NP_001280744.1
ALDH1A3-AS1	NR_135827.1	n.480+8099G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1466+2223C>T		intron_variant	Intron 12 of 12	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81035 AN: 151928 Hom.: 22081 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.533 AC: 81091 AN: 152046 Hom.: 22091 Cov.: 32 AF XY: 0.539 AC XY: 40056 AN XY: 74318

African (AFR) AF: 0.439 AC: 18203 AN: 41470

American (AMR) AF: 0.511 AC: 7814 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2124 AN: 3468

East Asian (EAS) AF: 0.693 AC: 3586 AN: 5174

South Asian (SAS) AF: 0.715 AC: 3453 AN: 4826

European-Finnish (FIN) AF: 0.577 AC: 6087 AN: 10550

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.558 AC: 37945 AN: 67960

Other (OTH) AF: 0.539 AC: 1137 AN: 2110

Alfa AF: 0.553 Hom.: 38880

Bravo AF: 0.519

Asia WGS AF: 0.699 AC: 2432 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	0.74
DANN	Benign	0.66
PhyloP100		-0.89
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: rs3803428; hg19: chr15-101450910;