chr15-100903225-C-T

Variant names:

• chr15-100903225-C-T
• rs4246326
• NM_000693.4:c.1069-2298C>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.1069-2298C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 148,276 control chromosomes in the GnomAD database, including 1,396 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 0.098 (1396 hom., cov: 31)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	NM_000693.4	MANE Select	c.1069-2298C>T		intron	N/A	NP_000684.2	P47895
	ALDH1A3	NM_001293815.2		c.748-2298C>T		intron	N/A	NP_001280744.1	H0Y2X5
	ALDH1A3-AS1	NR_135827.1		n.481-7159G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.1069-2298C>T		intron	N/A	ENSP00000332256.5	P47895
	ALDH1A3	ENST00000346623.6	TSL:1	c.748-2298C>T		intron	N/A	ENSP00000343294.6	H0Y2X5
	ALDH1A3	ENST00000856095.1		c.1168-2298C>T		intron	N/A	ENSP00000526154.1

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14459 AN: 148140 Hom.: 1387 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0146

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.0641

Gnomad EAS AF: 0.0717

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.0978 AC: 14497 AN: 148276 Hom.: 1396 Cov.: 31 AF XY: 0.0990 AC XY: 7159 AN XY: 72292

African (AFR) AF: 0.254 AC: 10309 AN: 40604

American (AMR) AF: 0.0601 AC: 892 AN: 14830

Ashkenazi Jewish (ASJ) AF: 0.0641 AC: 220 AN: 3430

East Asian (EAS) AF: 0.0712 AC: 342 AN: 4800

South Asian (SAS) AF: 0.0554 AC: 249 AN: 4494

European-Finnish (FIN) AF: 0.0565 AC: 554 AN: 9806

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0253 AC: 1697 AN: 67072

Other (OTH) AF: 0.0951 AC: 196 AN: 2060

Alfa AF: 0.0451 Hom.: 649

Bravo AF: 0.103

Asia WGS AF: 0.0610 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4246326; hg19: chr15-101443430;