rs14226

Variant names:

• chr15-100916112-G-A
• rs14226
• NM_000693.4:c.*1339G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000693.4(ALDH1A3):​c.*1339G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,146 control chromosomes in the GnomAD database, including 2,717 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 0.17 (2717 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ALDH1A3 NM_000693.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	NM_000693.4	MANE Select	c.*1339G>A		3_prime_UTR	Exon 13 of 13	NP_000684.2
	ALDH1A3	NM_001293815.2		c.*1339G>A		3_prime_UTR	Exon 10 of 10	NP_001280744.1
	ALDH1A3-AS1	NR_135827.1		n.480+2692C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.*1339G>A		3_prime_UTR	Exon 13 of 13	ENSP00000332256.5
	ALDH1A3	ENST00000346623.6	TSL:1	c.*1339G>A		3_prime_UTR	Exon 10 of 10	ENSP00000343294.6
	ALDH1A3-AS1	ENST00000560068.2	TSL:1	n.491-132C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26001 AN: 152026 Hom.: 2715 Cov.: 33

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.171 AC: 26017 AN: 152144 Hom.: 2717 Cov.: 33 AF XY: 0.174 AC XY: 12977 AN XY: 74394

African (AFR) AF: 0.0786 AC: 3263 AN: 41494

American (AMR) AF: 0.230 AC: 3511 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2300 AN: 5180

South Asian (SAS) AF: 0.166 AC: 802 AN: 4824

European-Finnish (FIN) AF: 0.199 AC: 2106 AN: 10582

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.190 AC: 12912 AN: 67990

Other (OTH) AF: 0.167 AC: 353 AN: 2112

Alfa AF: 0.185 Hom.: 5158

Bravo AF: 0.172

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.55
PhyloP100		-1.3
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: rs14226; hg19: chr15-101456317;