rs4646690

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-100914804-G-C
• chr15-100914804-G-A
• chr15-100914804-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	NM_000693.4	MANE Select	c.*31G>C		3_prime_UTR	Exon 13 of 13	NP_000684.2	P47895
	ALDH1A3	NM_001293815.2		c.*31G>C		3_prime_UTR	Exon 10 of 10	NP_001280744.1	H0Y2X5
	ALDH1A3-AS1	NR_135828.1		n.1657C>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.*31G>C		3_prime_UTR	Exon 13 of 13	ENSP00000332256.5	P47895
	ALDH1A3	ENST00000346623.6	TSL:1	c.*31G>C		3_prime_UTR	Exon 10 of 10	ENSP00000343294.6	H0Y2X5
	ALDH1A3-AS1	ENST00000560068.2	TSL:1	n.1667C>G		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.0580 AC: 14434 AN: 249020 AF XY: 0.0550

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 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

African (AFR) AF: 0.291 AC: 9692 AN: 33316

American (AMR) AF: 0.0390 AC: 1738 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 1947 AN: 26074

East Asian (EAS) AF: 0.0722 AC: 2863 AN: 39646

South Asian (SAS) AF: 0.0533 AC: 4577 AN: 85886

European-Finnish (FIN) AF: 0.0458 AC: 2429 AN: 52988

Middle Eastern (MID) AF: 0.117 AC: 672 AN: 5752

European-Non Finnish (NFE) AF: 0.0298 AC: 32887 AN: 1105340

Other (OTH) AF: 0.0593 AC: 3569 AN: 60166

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

African (AFR) AF: 0.281 AC: 11665 AN: 41488

American (AMR) AF: 0.0656 AC: 1003 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3470

East Asian (EAS) AF: 0.0670 AC: 347 AN: 5180

South Asian (SAS) AF: 0.0577 AC: 278 AN: 4822

European-Finnish (FIN) AF: 0.0540 AC: 571 AN: 10580

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0314 AC: 2136 AN: 68020

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0362 Hom.: 100

Bravo AF: 0.116

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.67
PhyloP100		0.42
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: rs4646690; hg19: chr15-101455009;