Variant chr9-72911950-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.828

Variant links:

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]

ALDH1A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1041 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A1	NM_000689.5 linkuse as main transcript	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 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.00768

AC XY:

1042

AN XY:

135608

show subpopulations

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.:

AF XY:

0.0108

AC XY:

7872

AN XY:

727012

show subpopulations

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.:

Cov.:

AF XY:

0.00605

AC XY:

450

AN XY:

74426

show subpopulations

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.:

Bravo

AF:

0.00660

Asia WGS

AF:

0.00173

AC:

AN:

3476

EpiCase

AF:

0.0111

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 18, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over