NM_000693.4:c.1391+491G>T

Variant names:

• chr15-100907769-G-T
• rs11854028
• NM_000693.4:c.1391+491G>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.1391+491G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,148 control chromosomes in the GnomAD database, including 24,030 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 0.56 (24030 hom., cov: 28)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.1391+491G>T		intron_variant	Intron 11 of 12	ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.1070+491G>T		intron_variant	Intron 8 of 9		NP_001280744.1
ALDH1A3-AS1	NR_135827.1	n.480+11035C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1391+491G>T		intron_variant	Intron 11 of 12	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.561 AC: 84783 AN: 151036 Hom.: 23994 Cov.: 28

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.562 AC: 84874 AN: 151148 Hom.: 24030 Cov.: 28 AF XY: 0.566 AC XY: 41772 AN XY: 73788

African (AFR) AF: 0.532 AC: 21896 AN: 41130

American (AMR) AF: 0.521 AC: 7919 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2204 AN: 3466

East Asian (EAS) AF: 0.693 AC: 3557 AN: 5130

South Asian (SAS) AF: 0.720 AC: 3433 AN: 4770

European-Finnish (FIN) AF: 0.576 AC: 5937 AN: 10302

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.560 AC: 37985 AN: 67858

Other (OTH) AF: 0.572 AC: 1202 AN: 2102

Alfa AF: 0.560 Hom.: 72963

Bravo AF: 0.551

Asia WGS AF: 0.727 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.11
PhyloP100		-0.30
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: rs11854028; hg19: chr15-101447974; COSMIC: COSV60903481; COSMIC: COSV60903481;