rs4646683

Positions:

• chr15-100906775-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000693.4(ALDH1A3):​c.1234-346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 152,126 control chromosomes in the GnomAD database, including 1,462 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 (1462 hom., cov: 33)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.1234-346C>T		intron_variant		ENST00000329841.10	NP_000684.2
ALDH1A3-AS1	NR_135827.1	n.481-10709G>A		intron_variant, non_coding_transcript_variant
ALDH1A3	NM_001293815.2	c.913-346C>T		intron_variant			NP_001280744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1234-346C>T		intron_variant		1	NM_000693.4	ENSP00000332256	P1
ALDH1A3-AS1	ENST00000656756.1	n.589-10709G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14852 AN: 152008 Hom.: 1450 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0600

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0965

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

GnomAD4 genome AF: 0.0979 AC: 14900 AN: 152126 Hom.: 1462 Cov.: 33 AF XY: 0.0989 AC XY: 7359 AN XY: 74380

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.0599

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.0667

Gnomad4 SAS AF: 0.0544

Gnomad4 FIN AF: 0.0536

Gnomad4 NFE AF: 0.0261

Gnomad4 OTH AF: 0.0959

Alfa AF: 0.0396 Hom.: 376

Bravo AF: 0.105

Asia WGS AF: 0.0620 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.87
DANN	Benign	0.35

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: rs4646683; hg19: chr15-101446980;