9-72911950-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000689.5(ALDH1A1):c.1200+8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,613,682 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (5 hom., cov: 32)
  • Exomes 𝑓: 0.011 (116 hom.)
• Consequence: ALDH1A1 NM_000689.5 splice_region, intron
• Scores: Splicing: ADA: 0.00007654
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.828

Genes affected

ALDH1A1 (HGNC:402): (aldehyde dehydrogenase 1 family member A1) The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 9-72911950-C-A is Benign according to our data. Variant chr9-72911950-C-A is described in ClinVar as [Benign]. Clinvar id is 773509.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1040 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A1	NM_000689.5	c.1200+8G>T		splice_region_variant, intron_variant		ENST00000297785.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1200+8G>T		splice_region_variant, intron_variant		1	NM_000689.5	P1

Frequencies

GnomAD3 genomes AF: 0.00684 AC: 1040 AN: 152130 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00577

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00717 AC: 1799 AN: 250916 Hom.: 8 AF XY: 0.00768 AC XY: 1042 AN XY: 135608

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.00426

Gnomad ASJ exome AF: 0.00974

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00516

Gnomad FIN exome AF: 0.00305

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.00637

GnomAD4 exome AF: 0.0109 AC: 15946 AN: 1461434 Hom.: 116 Cov.: 31 AF XY: 0.0108 AC XY: 7872 AN XY: 727012

Gnomad4 AFR exome AF: 0.00170

Gnomad4 AMR exome AF: 0.00436

Gnomad4 ASJ exome AF: 0.00930

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00586

Gnomad4 FIN exome AF: 0.00309

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.00805

GnomAD4 genome AF: 0.00684 AC: 1041 AN: 152248 Hom.: 5 Cov.: 32 AF XY: 0.00605 AC XY: 450 AN XY: 74426

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.0108 Hom.: 17

Bravo AF: 0.00660

Asia WGS AF: 0.00173 AC: 6 AN: 3476

EpiCase AF: 0.0111

EpiControl AF: 0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	8.4
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000077
dbscSNV1_RF	Benign	0.0
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: rs8187974; hg19: chr9-75526866;