chr15-100902231-C-T

Variant names:

• chr15-100902231-C-T
• rs4646678
• NM_000693.4:c.1068+1472C>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.1068+1472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,104 control chromosomes in the GnomAD database, including 2,552 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 0.16 (2552 hom., cov: 33)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.1068+1472C>T		intron_variant	Intron 9 of 12	ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.747+1472C>T		intron_variant	Intron 6 of 9		NP_001280744.1
ALDH1A3-AS1	NR_135827.1	n.481-6165G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1068+1472C>T		intron_variant	Intron 9 of 12	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24427 AN: 151986 Hom.: 2550 Cov.: 33

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.161 AC: 24425 AN: 152104 Hom.: 2552 Cov.: 33 AF XY: 0.164 AC XY: 12217 AN XY: 74356

African (AFR) AF: 0.0511 AC: 2119 AN: 41494

American (AMR) AF: 0.223 AC: 3412 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3468

East Asian (EAS) AF: 0.442 AC: 2276 AN: 5154

South Asian (SAS) AF: 0.166 AC: 799 AN: 4806

European-Finnish (FIN) AF: 0.198 AC: 2097 AN: 10592

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12617 AN: 67994

Other (OTH) AF: 0.159 AC: 336 AN: 2108

Alfa AF: 0.178 Hom.: 4316

Bravo AF: 0.160

Asia WGS AF: 0.290 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.75
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs4646678; hg19: chr15-101442436; COSMIC: COSV60901167;