rs4646681

Positions:

• chr15-100904713-C-G

Variant summary

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

The NM_000693.4(ALDH1A3):​c.1069-810C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 152,208 control chromosomes in the GnomAD database, including 1,535 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 0.10 (1535 hom., cov: 33)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.1069-810C>G		intron_variant		ENST00000329841.10	NP_000684.2
ALDH1A3-AS1	NR_135827.1	n.481-8647G>C		intron_variant, non_coding_transcript_variant
ALDH1A3	NM_001293815.2	c.748-810C>G		intron_variant			NP_001280744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1069-810C>G		intron_variant		1	NM_000693.4	ENSP00000332256	P1
ALDH1A3-AS1	ENST00000656756.1	n.589-8647G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15119 AN: 152090 Hom.: 1524 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0251

Gnomad OTH AF: 0.0971

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

GnomAD4 genome AF: 0.0996 AC: 15164 AN: 152208 Hom.: 1535 Cov.: 33 AF XY: 0.101 AC XY: 7482 AN XY: 74434

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.0591

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.0666

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0251

Gnomad4 OTH AF: 0.0966

Alfa AF: 0.0668 Hom.: 111

Bravo AF: 0.107

Asia WGS AF: 0.0630 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.84
DANN	Benign	0.48

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: rs4646681; hg19: chr15-101444918;