rs3796191

Variant names:

• chr3-126153541-A-G
• rs3796191
• NM_012190.4:c.761T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012190.4(ALDH1L1):​c.761T>C​(p.Leu254Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 1,614,118 control chromosomes in the GnomAD database, including 2,344 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.058 (311 hom., cov: 33)
  • Exomes 𝑓: 0.048 (2033 hom.)
• Consequence: ALDH1L1 NM_012190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048755407).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.761T>C	p.Leu254Pro	missense_variant	Exon 7 of 23	ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.761T>C	p.Leu254Pro	missense_variant	Exon 7 of 23	1	NM_012190.4	ENSP00000377083.3

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8744 AN: 152158 Hom.: 306 Cov.: 33

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.0777

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0522

GnomAD2 exomes AF: 0.0579 AC: 14541 AN: 251258 AF XY: 0.0539

Gnomad AFR exome AF: 0.0681

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.0211

Gnomad EAS exome AF: 0.0171

Gnomad FIN exome AF: 0.0759

Gnomad NFE exome AF: 0.0438

Gnomad OTH exome AF: 0.0576

GnomAD4 exome AF: 0.0475 AC: 69457 AN: 1461842 Hom.: 2033 Cov.: 31 AF XY: 0.0469 AC XY: 34078 AN XY: 727234

African (AFR) AF: 0.0668 AC: 2236 AN: 33478

American (AMR) AF: 0.126 AC: 5633 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 580 AN: 26134

East Asian (EAS) AF: 0.0286 AC: 1134 AN: 39700

South Asian (SAS) AF: 0.0475 AC: 4099 AN: 86254

European-Finnish (FIN) AF: 0.0752 AC: 4018 AN: 53402

Middle Eastern (MID) AF: 0.0413 AC: 238 AN: 5768

European-Non Finnish (NFE) AF: 0.0439 AC: 48853 AN: 1111994

Other (OTH) AF: 0.0441 AC: 2666 AN: 60392

GnomAD4 genome AF: 0.0576 AC: 8766 AN: 152276 Hom.: 311 Cov.: 33 AF XY: 0.0591 AC XY: 4398 AN XY: 74452

African (AFR) AF: 0.0658 AC: 2733 AN: 41562

American (AMR) AF: 0.0977 AC: 1494 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3472

East Asian (EAS) AF: 0.0183 AC: 95 AN: 5178

South Asian (SAS) AF: 0.0550 AC: 265 AN: 4820

European-Finnish (FIN) AF: 0.0777 AC: 824 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0463 AC: 3152 AN: 68022

Other (OTH) AF: 0.0516 AC: 109 AN: 2112

Alfa AF: 0.0464 Hom.: 874

Bravo AF: 0.0592

TwinsUK AF: 0.0450 AC: 167

ALSPAC AF: 0.0415 AC: 160

ESP6500AA AF: 0.0690 AC: 304

ESP6500EA AF: 0.0445 AC: 383

ExAC AF: 0.0553 AC: 6719

Asia WGS AF: 0.0450 AC: 157 AN: 3478

EpiCase AF: 0.0412

EpiControl AF: 0.0389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.041	.;.;T;.;T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.68	T;T;.;T;T;.
MetaRNN	Benign	0.0049	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N;.;N;.;N;N
PhyloP100		2.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.28	.;N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.39	.;T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T;T
Polyphen		0.0	.;.;B;.;B;.
Vest4		0.10
MPC		0.60
ClinPred		0.011	T
GERP RS		2.4
Varity_R		0.46
gMVP		0.61
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3796191; hg19: chr3-125872384;