3-126130395-G-A

Variant names:

• chr3-126130395-G-A
• rs2002287
• NM_012190.4:c.1624-102C>T

Variant summary

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

The NM_012190.4(ALDH1L1):​c.1624-102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,066,462 control chromosomes in the GnomAD database, including 217,628 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 0.63 (30780 hom., cov: 34)
  • Exomes 𝑓: 0.64 (186848 hom.)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 13 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 (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 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.1624-102C>T		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.1654-102C>T		intron	N/A	NP_001257293.1
	ALDH1L1	NM_001270365.2		c.1321-102C>T		intron	N/A	NP_001257294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	ENST00000393434.7	TSL:1 MANE Select	c.1624-102C>T		intron	N/A	ENSP00000377083.3
	ALDH1L1	ENST00000273450.7	TSL:1	c.1654-102C>T		intron	N/A	ENSP00000273450.3
	ALDH1L1	ENST00000393431.6	TSL:1	c.1473-102C>T		intron	N/A	ENSP00000377081.2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96550 AN: 152038 Hom.: 30765 Cov.: 34

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.635 AC: 580769 AN: 914306 Hom.: 186848 AF XY: 0.633 AC XY: 286313 AN XY: 452618

African (AFR) AF: 0.654 AC: 12918 AN: 19742

American (AMR) AF: 0.480 AC: 7533 AN: 15700

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 10254 AN: 14958

East Asian (EAS) AF: 0.570 AC: 16201 AN: 28422

South Asian (SAS) AF: 0.478 AC: 19841 AN: 41514

European-Finnish (FIN) AF: 0.619 AC: 25342 AN: 40926

Middle Eastern (MID) AF: 0.695 AC: 2989 AN: 4302

European-Non Finnish (NFE) AF: 0.649 AC: 460556 AN: 709214

Other (OTH) AF: 0.636 AC: 25135 AN: 39528

GnomAD4 genome AF: 0.635 AC: 96608 AN: 152156 Hom.: 30780 Cov.: 34 AF XY: 0.629 AC XY: 46807 AN XY: 74366

African (AFR) AF: 0.652 AC: 27051 AN: 41518

American (AMR) AF: 0.578 AC: 8841 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2378 AN: 3472

East Asian (EAS) AF: 0.582 AC: 3004 AN: 5160

South Asian (SAS) AF: 0.490 AC: 2359 AN: 4818

European-Finnish (FIN) AF: 0.613 AC: 6493 AN: 10592

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44322 AN: 67982

Other (OTH) AF: 0.660 AC: 1392 AN: 2110

Alfa AF: 0.567 Hom.: 3063

Bravo AF: 0.635

Asia WGS AF: 0.569 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.53
PhyloP100		-1.3
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: rs2002287; hg19: chr3-125849238;