9-72911950-C-A

Variant names:

• chr9-72911950-C-A
• rs8187974
• NM_000689.5:c.1200+8G>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.828
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 773509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1041 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000689.5. 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
	ALDH1A1	NM_000689.5	MANE Select	c.1200+8G>T		splice_region intron	N/A	NP_000680.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.1200+8G>T		splice_region intron	N/A	ENSP00000297785.3	P00352
	ALDH1A1	ENST00000856212.1		c.1290+8G>T		splice_region intron	N/A	ENSP00000526271.1
	ALDH1A1	ENST00000966555.1		c.1269+8G>T		splice_region intron	N/A	ENSP00000636614.1

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

GnomAD2 exomes AF: 0.00717 AC: 1799 AN: 250916 AF XY: 0.00768

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 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

African (AFR) AF: 0.00170 AC: 57 AN: 33452

American (AMR) AF: 0.00436 AC: 195 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00930 AC: 243 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39678

South Asian (SAS) AF: 0.00586 AC: 505 AN: 86228

European-Finnish (FIN) AF: 0.00309 AC: 165 AN: 53412

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5762

European-Non Finnish (NFE) AF: 0.0128 AC: 14274 AN: 1111714

Other (OTH) AF: 0.00805 AC: 486 AN: 60370

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

African (AFR) AF: 0.00224 AC: 93 AN: 41560

American (AMR) AF: 0.00582 AC: 89 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4822

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0112 AC: 765 AN: 68014

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.0107 Hom.: 19

Bravo AF: 0.00660

Asia WGS AF: 0.00173 AC: 6 AN: 3476

EpiCase AF: 0.0111

EpiControl AF: 0.0129

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.4
DANN	Benign	0.68
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs8187974; hg19: chr9-75526866;