rs7215

Variant names:

• chr17-19677181-A-G
• rs7215
• NM_000382.3:c.*1609A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-19677181-A-G
• chr17-19677181-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000382.3(ALDH3A2):​c.*1609A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,104 control chromosomes in the GnomAD database, including 21,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21386 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ALDH3A2 NM_000382.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.21
• Publications: 13 publications found

Genes affected

ALDH3A2 (HGNC:403): (aldehyde dehydrogenase 3 family member A2) Aldehyde dehydrogenase isozymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This gene product catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. Mutations in the gene cause Sjogren-Larsson syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ALDH3A2 Gene-Disease associations (from GenCC):

• Sjogren-Larsson syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-19677181-A-G is Benign according to our data. Variant chr17-19677181-A-G is described in ClinVar as Benign. ClinVar VariationId is 322237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000382.3. 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
	ALDH3A2	NM_000382.3	MANE Select	c.*1609A>G		3_prime_UTR	Exon 10 of 10	NP_000373.1	P51648-1
	ALDH3A2	NM_001031806.2		c.*1665A>G		3_prime_UTR	Exon 11 of 11	NP_001026976.1	P51648-2
	ALDH3A2	NM_001369136.1		c.*1665A>G		3_prime_UTR	Exon 12 of 12	NP_001356065.1	P51648-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3A2	ENST00000176643.11	TSL:1 MANE Select	c.*1609A>G		3_prime_UTR	Exon 10 of 10	ENSP00000176643.6	P51648-1
	ALDH3A2	ENST00000339618.8	TSL:1	c.*1665A>G		3_prime_UTR	Exon 11 of 11	ENSP00000345774.4	P51648-2
	ALDH3A2	ENST00000579855.5	TSL:5	c.*1609A>G		3_prime_UTR	Exon 11 of 11	ENSP00000463637.1	P51648-1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78656 AN: 151984 Hom.: 21360 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.500 AC: 1 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: 0.500 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

GnomAD4 genome AF: 0.518 AC: 78729 AN: 152102 Hom.: 21386 Cov.: 33 AF XY: 0.524 AC XY: 38964 AN XY: 74332

African (AFR) AF: 0.386 AC: 16000 AN: 41482

American (AMR) AF: 0.646 AC: 9879 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3464

East Asian (EAS) AF: 0.908 AC: 4704 AN: 5182

South Asian (SAS) AF: 0.667 AC: 3215 AN: 4820

European-Finnish (FIN) AF: 0.479 AC: 5066 AN: 10568

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36458 AN: 67982

Other (OTH) AF: 0.521 AC: 1101 AN: 2112

Alfa AF: 0.538 Hom.: 66627

Bravo AF: 0.522

Asia WGS AF: 0.780 AC: 2710 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Sjögren-Larsson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		-1.2
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: rs7215; hg19: chr17-19580494; COSMIC: COSV51568524; COSMIC: COSV51568524;