rs2886059

Variant names:

• chr3-126146923-C-A
• rs2886059
• NM_012190.4:c.988G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-126146923-C-A
• chr3-126146923-C-G

Variant summary

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

The NM_012190.4(ALDH1L1):​c.988G>T​(p.Val330Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,612,746 control chromosomes in the GnomAD database, including 25,629 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.22 (4275 hom., cov: 32)
  • Exomes 𝑓: 0.16 (21354 hom.)
• Consequence: ALDH1L1 NM_012190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 33 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=0.012716591).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012190.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	NM_012190.4	MANE Select	c.988G>T	p.Val330Phe	missense	Exon 9 of 23	NP_036322.2
	ALDH1L1	NM_001270364.2		c.1018G>T	p.Val340Phe	missense	Exon 9 of 23	NP_001257293.1
	ALDH1L1	NM_001270365.2		c.685G>T	p.Val229Phe	missense	Exon 7 of 21	NP_001257294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	ENST00000393434.7	TSL:1 MANE Select	c.988G>T	p.Val330Phe	missense	Exon 9 of 23	ENSP00000377083.3
	ALDH1L1	ENST00000273450.7	TSL:1	c.1018G>T	p.Val340Phe	missense	Exon 9 of 23	ENSP00000273450.3
	ALDH1L1	ENST00000393431.6	TSL:1	c.988G>T	p.Val330Phe	missense	Exon 9 of 21	ENSP00000377081.2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32934 AN: 151998 Hom.: 4265 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.224

GnomAD2 exomes AF: 0.159 AC: 39687 AN: 249486 AF XY: 0.154

Gnomad AFR exome AF: 0.369

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.212

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.165 AC: 240835 AN: 1460628 Hom.: 21354 Cov.: 32 AF XY: 0.162 AC XY: 117647 AN XY: 726506

African (AFR) AF: 0.365 AC: 12209 AN: 33452

American (AMR) AF: 0.118 AC: 5262 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4121 AN: 26112

East Asian (EAS) AF: 0.246 AC: 9750 AN: 39678

South Asian (SAS) AF: 0.0958 AC: 8235 AN: 85994

European-Finnish (FIN) AF: 0.122 AC: 6526 AN: 53342

Middle Eastern (MID) AF: 0.166 AC: 957 AN: 5760

European-Non Finnish (NFE) AF: 0.165 AC: 182988 AN: 1111294

Other (OTH) AF: 0.179 AC: 10787 AN: 60366

GnomAD4 genome AF: 0.217 AC: 32973 AN: 152118 Hom.: 4275 Cov.: 32 AF XY: 0.212 AC XY: 15797 AN XY: 74356

African (AFR) AF: 0.364 AC: 15116 AN: 41474

American (AMR) AF: 0.183 AC: 2791 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1119 AN: 5154

South Asian (SAS) AF: 0.106 AC: 512 AN: 4822

European-Finnish (FIN) AF: 0.118 AC: 1250 AN: 10582

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10997 AN: 68010

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.182 Hom.: 8610

Bravo AF: 0.227

TwinsUK AF: 0.160 AC: 592

ALSPAC AF: 0.157 AC: 607

ESP6500AA AF: 0.360 AC: 1587

ESP6500EA AF: 0.164 AC: 1412

ExAC AF: 0.165 AC: 19987

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.021
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.033
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.25	B
Vest4		0.39
MPC		0.26
ClinPred		0.058	T
GERP RS		0.56
Varity_R		0.39
gMVP		0.72
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2886059; hg19: chr3-125865766; COSMIC: COSV56417895; COSMIC: COSV56417895;