15-100914804-G-C

Variant names:

• chr15-100914804-G-C
• rs4646690
• NM_000693.4:c.*31G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000693.4(ALDH1A3):​c.*31G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,605,850 control chromosomes in the GnomAD database, including 4,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1795 hom., cov: 33)
  • Exomes 𝑓: 0.042 (2536 hom.)
• Consequence: ALDH1A3 NM_000693.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.418

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-100914804-G-C is Benign according to our data. Variant chr15-100914804-G-C is described in ClinVar as [Benign]. Clinvar id is 1183310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.*31G>C		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.*31G>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16475 AN: 152054 Hom.: 1785 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0657

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.100

GnomAD3 exomes AF: 0.0580 AC: 14434 AN: 249020 Hom.: 866 AF XY: 0.0550 AC XY: 7400 AN XY: 134656

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.0358

Gnomad ASJ exome AF: 0.0786

Gnomad EAS exome AF: 0.0631

Gnomad SAS exome AF: 0.0532

Gnomad FIN exome AF: 0.0456

Gnomad NFE exome AF: 0.0334

Gnomad OTH exome AF: 0.0529

GnomAD4 exome AF: 0.0415 AC: 60374 AN: 1453678 Hom.: 2536 Cov.: 27 AF XY: 0.0414 AC XY: 29976 AN XY: 723582

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.0390

Gnomad4 ASJ exome AF: 0.0747

Gnomad4 EAS exome AF: 0.0722

Gnomad4 SAS exome AF: 0.0533

Gnomad4 FIN exome AF: 0.0458

Gnomad4 NFE exome AF: 0.0298

Gnomad4 OTH exome AF: 0.0593

GnomAD4 genome AF: 0.109 AC: 16512 AN: 152172 Hom.: 1795 Cov.: 33 AF XY: 0.108 AC XY: 8047 AN XY: 74404

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.0670

Gnomad4 SAS AF: 0.0577

Gnomad4 FIN AF: 0.0540

Gnomad4 NFE AF: 0.0314

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.0362 Hom.: 100

Bravo AF: 0.116

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.67

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: rs4646690; hg19: chr15-101455009;