dbSNP rs1127717: ALDH1L1:p.Asp793Gly (chr3-126107216-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012190.4(ALDH1L1):c.2378A>G(p.Asp793Gly) variant causes a missense change. The variant allele was found at a frequency of 0.202 in 1,613,530 control chromosomes in the GnomAD database, including 33,783 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3102 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30681 hom. )

Consequence

ALDH1L1
NM_012190.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98

Variant links:

Genes affected

ALDH1L1 (HGNC:3978): (aldehyde dehydrogenase 1 family member L1) The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression. There is an antisense transcript that overlaps on the opposite strand with this gene locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ALDH1L1 links:

ALDH1L1-AS1 (HGNC:40244): (ALDH1L1 antisense RNA 1)

ALDH1L1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026737452).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4 link	c.2378A>G	p.Asp793Gly	missense_variant	Exon 21 of 23	ENST00000393434.7	NP_036322.2	O75891-1Q53H87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7 link	c.2378A>G	p.Asp793Gly	missense_variant	Exon 21 of 23	1	NM_012190.4	ENSP00000377083.3		O75891-1

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30131

AN:

152116

Hom.:

3099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.185

AC:

46395

AN:

251432

Hom.:

4650

AF XY:

0.190

AC XY:

25832

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.202

AC:

295779

AN:

1461296

Hom.:

30681

Cov.:

AF XY:

0.204

AC XY:

148333

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.198

AC:

30142

AN:

152234

Hom.:

3102

Cov.:

AF XY:

0.194

AC XY:

14412

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.208

Hom.:

8307

Bravo

AF:

0.202

TwinsUK

AF:

0.201

AC:

746

ALSPAC

AF:

0.199

AC:

767

ESP6500AA

AF:

0.213

AC:

940

ESP6500EA

AF:

0.216

AC:

1855

ExAC

AF:

0.189

AC:

22887

Asia WGS

AF:

0.210

AC:

729

AN:

3478

EpiCase

AF:

0.218

EpiControl

AF:

0.222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.49

.;T;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.68

T;.;T;T

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L;.;L

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-4.1

D;D;D;D

REVEL

Benign

0.15

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.0030

.;B;.;B

Vest4

0.14

MPC

0.25

ClinPred

0.019

GERP RS

4.0

Varity_R

0.30

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over