rs61757679

Variant names:

• chr15-100895956-G-A
• rs61757679
• NM_000693.4:c.690G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-100895956-G-A
• chr15-100895956-G-C
• chr15-100895956-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_000693.4(ALDH1A3):​c.690G>A​(p.Val230Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,560 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: ALDH1A3 NM_000693.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.912
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 15-100895956-G-A is Benign according to our data. Variant chr15-100895956-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 473869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.912 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000748 (114/152352) while in subpopulation NFE AF = 0.00121 (82/68022). AF 95% confidence interval is 0.000995. There are 0 homozygotes in GnomAd4. There are 54 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.690G>A	p.Val230Val	synonymous	Exon 7 of 13	NP_000684.2	P47895
	ALDH1A3	NM_001293815.2		c.369G>A	p.Val123Val	synonymous	Exon 4 of 10	NP_001280744.1	H0Y2X5
	ALDH1A3-AS1	NR_135827.1		n.591C>T		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.690G>A	p.Val230Val	synonymous	Exon 7 of 13	ENSP00000332256.5	P47895
	ALDH1A3	ENST00000346623.6	TSL:1	c.369G>A	p.Val123Val	synonymous	Exon 4 of 10	ENSP00000343294.6	H0Y2X5
	ALDH1A3	ENST00000856095.1		c.690G>A	p.Val230Val	synonymous	Exon 7 of 14	ENSP00000526154.1

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 114 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000792 AC: 198 AN: 249920 AF XY: 0.000851

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00124

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.00104 AC: 1524 AN: 1461208 Hom.: 1 Cov.: 30 AF XY: 0.00104 AC XY: 755 AN XY: 726790

African (AFR) AF: 0.000149 AC: 5 AN: 33468

American (AMR) AF: 0.00105 AC: 47 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85980

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53394

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.00125 AC: 1389 AN: 1111748

Other (OTH) AF: 0.000712 AC: 43 AN: 60364

GnomAD4 genome AF: 0.000748 AC: 114 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.000725 AC XY: 54 AN XY: 74506

African (AFR) AF: 0.000361 AC: 15 AN: 41580

American (AMR) AF: 0.000849 AC: 13 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00121 AC: 82 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00102 Hom.: 1

Bravo AF: 0.000850

EpiCase AF: 0.00131

EpiControl AF: 0.00107

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ALDH1A3-related disorder (1)
-	-	1	Isolated microphthalmia 8 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		0.91
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61757679; hg19: chr15-101436161;