rs2305230

Positions:

• chr3-126137852-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012190.4(ALDH1L1):​c.1185G>T​(p.Leu395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,982 control chromosomes in the GnomAD database, including 26,561 homozygotes. In-silico tool predicts 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 (4682 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21879 hom.)
• Consequence: ALDH1L1 NM_012190.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.332 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.1185G>T	p.Leu395=	synonymous_variant	10/23	ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1185G>T	p.Leu395=	synonymous_variant	10/23	1	NM_012190.4	ENSP00000377083	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34083 AN: 152066 Hom.: 4670 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.228

GnomAD3 exomes AF: 0.163 AC: 40863 AN: 251244 Hom.: 4016 AF XY: 0.157 AC XY: 21353 AN XY: 135790

Gnomad AFR exome AF: 0.396

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.214

Gnomad SAS exome AF: 0.0988

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.166 AC: 243144 AN: 1461798 Hom.: 21879 Cov.: 32 AF XY: 0.163 AC XY: 118718 AN XY: 727188

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.0967

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.224 AC: 34128 AN: 152184 Hom.: 4682 Cov.: 33 AF XY: 0.220 AC XY: 16353 AN XY: 74400

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.230

Alfa AF: 0.174 Hom.: 4004

Bravo AF: 0.236

Asia WGS AF: 0.187 AC: 649 AN: 3478

EpiCase AF: 0.168

EpiControl AF: 0.169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.1
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2305230; hg19: chr3-125856695; COSMIC: COSV56417279;