rs2305230

Variant names:

• chr3-126137852-C-A
• rs2305230
• NM_012190.4:c.1185G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-126137852-C-A
• chr3-126137852-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012190.4(ALDH1L1):​c.1185G>T​(p.Leu395Leu) 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
• Publications: 27 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 -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 rank	MANE	Protein	UniProt
ALDH1L1	NM_012190.4	c.1185G>T	p.Leu395Leu	synonymous_variant	Exon 10 of 23	ENST00000393434.7	NP_036322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7	c.1185G>T	p.Leu395Leu	synonymous_variant	Exon 10 of 23	1	NM_012190.4	ENSP00000377083.3

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

GnomAD2 exomes AF: 0.163 AC: 40863 AN: 251244 AF XY: 0.157

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 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

African (AFR) AF: 0.392 AC: 13114 AN: 33478

American (AMR) AF: 0.120 AC: 5380 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4127 AN: 26132

East Asian (EAS) AF: 0.246 AC: 9773 AN: 39696

South Asian (SAS) AF: 0.0967 AC: 8341 AN: 86250

European-Finnish (FIN) AF: 0.124 AC: 6602 AN: 53418

Middle Eastern (MID) AF: 0.167 AC: 964 AN: 5758

European-Non Finnish (NFE) AF: 0.165 AC: 183873 AN: 1111956

Other (OTH) AF: 0.182 AC: 10970 AN: 60388

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

African (AFR) AF: 0.389 AC: 16132 AN: 41498

American (AMR) AF: 0.187 AC: 2858 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1128 AN: 5174

South Asian (SAS) AF: 0.107 AC: 514 AN: 4812

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10604

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11037 AN: 68010

Other (OTH) AF: 0.230 AC: 487 AN: 2116

Alfa AF: 0.179 Hom.: 5292

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
PhyloP100		-0.33
Mutation Taster		=100/0	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: rs2305230; hg19: chr3-125856695; COSMIC: COSV56417279;