15-100900009-G-C

Variant names:

• chr15-100900009-G-C
• rs4646672
• NM_000693.4:c.884-566G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.94).
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	NM_000693.4	MANE Select	c.884-566G>C		intron	N/A	NP_000684.2	P47895
	ALDH1A3	NM_001293815.2		c.563-566G>C		intron	N/A	NP_001280744.1	H0Y2X5
	ALDH1A3-AS1	NR_135827.1		n.481-3943C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.884-566G>C		intron	N/A	ENSP00000332256.5	P47895
	ALDH1A3	ENST00000346623.6	TSL:1	c.563-566G>C		intron	N/A	ENSP00000343294.6	H0Y2X5
	ALDH1A3	ENST00000856095.1		c.983-566G>C		intron	N/A	ENSP00000526154.1

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

African (AFR) AF: 0.0123 AC: 509 AN: 41510

American (AMR) AF: 0.00150 AC: 23 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5188

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00 Hom.: 479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.010
DANN	Benign	0.73
PhyloP100		-0.88

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: rs4646672; hg19: chr15-101440214;