chr3-126107216-T-C

Variant names:

• chr3-126107216-T-C
• rs1127717
• NM_012190.4:c.2378A>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.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. 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 0.20 (3102 hom., cov: 33)
  • Exomes 𝑓: 0.20 (30681 hom.)
• Consequence: ALDH1L1 NM_012190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 48 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

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.2378A>G	p.Asp793Gly	missense	Exon 21 of 23	NP_036322.2
	ALDH1L1	NM_001270364.2		c.2408A>G	p.Asp803Gly	missense	Exon 21 of 23	NP_001257293.1
	ALDH1L1	NM_001270365.2		c.2075A>G	p.Asp692Gly	missense	Exon 19 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.2378A>G	p.Asp793Gly	missense	Exon 21 of 23	ENSP00000377083.3
	ALDH1L1	ENST00000273450.7	TSL:1	c.2408A>G	p.Asp803Gly	missense	Exon 21 of 23	ENSP00000273450.3
	ALDH1L1	ENST00000393431.6	TSL:1	c.*609A>G		3_prime_UTR	Exon 19 of 21	ENSP00000377081.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30131 AN: 152116 Hom.: 3099 Cov.: 33

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

GnomAD2 exomes AF: 0.185 AC: 46395 AN: 251432 AF XY: 0.190

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 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.: 33 AF XY: 0.204 AC XY: 148333 AN XY: 727016

African (AFR) AF: 0.220 AC: 7376 AN: 33466

American (AMR) AF: 0.120 AC: 5364 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6775 AN: 26136

East Asian (EAS) AF: 0.130 AC: 5180 AN: 39698

South Asian (SAS) AF: 0.226 AC: 19532 AN: 86242

European-Finnish (FIN) AF: 0.127 AC: 6796 AN: 53366

Middle Eastern (MID) AF: 0.247 AC: 1425 AN: 5768

European-Non Finnish (NFE) AF: 0.207 AC: 230564 AN: 1111540

Other (OTH) AF: 0.212 AC: 12767 AN: 60362

GnomAD4 genome AF: 0.198 AC: 30142 AN: 152234 Hom.: 3102 Cov.: 33 AF XY: 0.194 AC XY: 14412 AN XY: 74432

African (AFR) AF: 0.220 AC: 9156 AN: 41536

American (AMR) AF: 0.169 AC: 2585 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 914 AN: 3468

East Asian (EAS) AF: 0.129 AC: 669 AN: 5170

South Asian (SAS) AF: 0.229 AC: 1105 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1303 AN: 10618

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13702 AN: 68006

Other (OTH) AF: 0.232 AC: 490 AN: 2112

Alfa AF: 0.206 Hom.: 14616

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.0
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.15
Sift	Benign	0.10	T
Sift4G	Benign	0.14	T
Polyphen		0.0030	B
Vest4		0.14
MPC		0.25
ClinPred		0.019	T
GERP RS		4.0
Varity_R		0.30
gMVP		0.80
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1127717; hg19: chr3-125826059; COSMIC: COSV56412084;