chr15-100916578-C-T

Variant names:

• chr15-100916578-C-T
• rs7045
• NM_000693.4:c.*1805C>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.*1805C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,208 control chromosomes in the GnomAD database, including 2,604 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 (2602 hom., cov: 33)
  • Exomes 𝑓: 0.27 (2 hom.)
• Consequence: ALDH1A3 NM_000693.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.*1805C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000329841.10	NP_000684.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.*1805C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24768 AN: 152060 Hom.: 2600 Cov.: 33

Gnomad AFR AF: 0.0523

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.267 AC: 8 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.292 AC XY: 7 AN XY: 24

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.267 AC: 8 AN: 30

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.163 AC: 24767 AN: 152178 Hom.: 2602 Cov.: 33 AF XY: 0.166 AC XY: 12378 AN XY: 74380

African (AFR) AF: 0.0521 AC: 2165 AN: 41528

American (AMR) AF: 0.228 AC: 3485 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 702 AN: 3466

East Asian (EAS) AF: 0.431 AC: 2232 AN: 5178

South Asian (SAS) AF: 0.170 AC: 821 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2097 AN: 10572

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12811 AN: 67990

Other (OTH) AF: 0.164 AC: 346 AN: 2116

Alfa AF: 0.177 Hom.: 6940

Bravo AF: 0.163

Asia WGS AF: 0.288 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		0.46
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: rs7045; hg19: chr15-101456783;