15-100900009-G-C

Position:

• chr15-100900009-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000693.4(ALDH1A3):​c.884-566G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 152,214 control chromosomes in the GnomAD database, including 4 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 0.0037 (4 hom., cov: 33)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00367 (559/152214) while in subpopulation AFR AF= 0.0123 (509/41510). AF 95% confidence interval is 0.0114. There are 4 homozygotes in gnomad4. There are 253 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.884-566G>C		intron_variant		ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.563-566G>C		intron_variant			NP_001280744.1
ALDH1A3-AS1	NR_135827.1	n.481-3943C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.884-566G>C		intron_variant		1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.00366 AC: 556 AN: 152096 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.00367 AC: 559 AN: 152214 Hom.: 4 Cov.: 33 AF XY: 0.00340 AC XY: 253 AN XY: 74416

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.010
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646672; hg19: chr15-101440214;