rs1800869

Variant names:

• chr17-19661321-C-G
• rs1800869
• NM_000382.3:c.940+53C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-19661321-C-G
• chr17-19661321-C-T

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.940+53C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,602,854 control chromosomes in the GnomAD database, including 50,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3577 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47277 hom.)
• Consequence: ALDH3A2 NM_000382.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.275
• Publications: 21 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: G2P, Myriad Women’s Health, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018155575).
• BP6: Variant 17-19661321-C-G is Benign according to our data. Variant chr17-19661321-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1184631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH3A2	NM_000382.3	c.940+53C>G		intron_variant	Intron 6 of 9	ENST00000176643.11	NP_000373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH3A2	ENST00000176643.11	c.940+53C>G		intron_variant	Intron 6 of 9	1	NM_000382.3	ENSP00000176643.6

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30327 AN: 151952 Hom.: 3572 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.190

GnomAD2 exomes AF: 0.240 AC: 60156 AN: 250216 AF XY: 0.238

Gnomad AFR exome AF: 0.0640

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.394

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.249 AC: 361771 AN: 1450784 Hom.: 47277 Cov.: 29 AF XY: 0.248 AC XY: 178917 AN XY: 722498

African (AFR) AF: 0.0618 AC: 2049 AN: 33136

American (AMR) AF: 0.301 AC: 13463 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3986 AN: 26042

East Asian (EAS) AF: 0.437 AC: 17317 AN: 39608

South Asian (SAS) AF: 0.220 AC: 18919 AN: 85964

European-Finnish (FIN) AF: 0.215 AC: 11460 AN: 53366

Middle Eastern (MID) AF: 0.106 AC: 608 AN: 5740

European-Non Finnish (NFE) AF: 0.254 AC: 280069 AN: 1102258

Other (OTH) AF: 0.232 AC: 13900 AN: 59998

GnomAD4 genome AF: 0.200 AC: 30347 AN: 152070 Hom.: 3577 Cov.: 32 AF XY: 0.201 AC XY: 14971 AN XY: 74330

African (AFR) AF: 0.0705 AC: 2927 AN: 41496

American (AMR) AF: 0.273 AC: 4168 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3472

East Asian (EAS) AF: 0.387 AC: 2005 AN: 5176

South Asian (SAS) AF: 0.240 AC: 1156 AN: 4812

European-Finnish (FIN) AF: 0.211 AC: 2218 AN: 10536

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.245 AC: 16680 AN: 67982

Other (OTH) AF: 0.193 AC: 407 AN: 2110

Alfa AF: 0.214 Hom.: 793

Bravo AF: 0.197

TwinsUK AF: 0.250 AC: 928

ALSPAC AF: 0.248 AC: 957

ExAC AF: 0.235 AC: 28562

Asia WGS AF: 0.274 AC: 951 AN: 3478

EpiCase AF: 0.229

EpiControl AF: 0.225

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sjögren-Larsson syndrome Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.5
DANN	Benign	0.68
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0018	T
PhyloP100		-0.28
GERP RS		2.2
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: rs1800869; hg19: chr17-19564634; COSMIC: COSV107187384; COSMIC: COSV107187384;