ENST00000560068.2:n.836C>T

Variant names:

• chr15-100915635-G-A
• rs1130738
• ENST00000560068.2:n.836C>T

Variant summary

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

The ENST00000560068.2(ALDH1A3-AS1):​n.836C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,038 control chromosomes in the GnomAD database, including 23,725 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 0.56 (23725 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALDH1A3-AS1 ENST00000560068.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 9 publications found

Genes affected

ALDH1A3-AS1 (HGNC:55416): (ALDH1A3 antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• isolated anophthalmia-microphthalmia syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• isolated microphthalmia 8

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.*862G>A		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.*862G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84333 AN: 151920 Hom.: 23711 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.553

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.555 AC: 84392 AN: 152038 Hom.: 23725 Cov.: 33 AF XY: 0.562 AC XY: 41779 AN XY: 74338

African (AFR) AF: 0.486 AC: 20137 AN: 41432

American (AMR) AF: 0.518 AC: 7914 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2138 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3593 AN: 5178

South Asian (SAS) AF: 0.717 AC: 3454 AN: 4816

European-Finnish (FIN) AF: 0.631 AC: 6667 AN: 10564

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38553 AN: 67984

Other (OTH) AF: 0.551 AC: 1162 AN: 2108

Alfa AF: 0.561 Hom.: 96843

Bravo AF: 0.539

Asia WGS AF: 0.701 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.83
PhyloP100		-1.1
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: rs1130738; hg19: chr15-101455840;