3-126167598-G-C

Variant names:

• chr3-126167598-G-C
• rs4646698
• NM_012190.4:c.-23-6596C>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.-23-6596C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 152,002 control chromosomes in the GnomAD database, including 119 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 0.016 (119 hom., cov: 32)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 0 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]

LOC105374083 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 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.-23-6596C>G		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.8-6596C>G		intron	N/A	NP_001257293.1
	ALDH1L1	NM_001270365.2		c.-23-6596C>G		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.-23-6596C>G		intron	N/A	ENSP00000377083.3
	ALDH1L1	ENST00000273450.7	TSL:1	c.8-6596C>G		intron	N/A	ENSP00000273450.3
	ALDH1L1	ENST00000393431.6	TSL:1	c.-23-6596C>G		intron	N/A	ENSP00000377081.2

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2499 AN: 151884 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00424

Gnomad OTH AF: 0.0144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0164 AC: 2497 AN: 152002 Hom.: 119 Cov.: 32 AF XY: 0.0195 AC XY: 1452 AN XY: 74280

African (AFR) AF: 0.00998 AC: 414 AN: 41474

American (AMR) AF: 0.0147 AC: 224 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.192 AC: 994 AN: 5176

South Asian (SAS) AF: 0.0258 AC: 124 AN: 4806

European-Finnish (FIN) AF: 0.0381 AC: 402 AN: 10552

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00424 AC: 288 AN: 67954

Other (OTH) AF: 0.0147 AC: 31 AN: 2104

Alfa AF: 0.00858 Hom.: 0

Bravo AF: 0.0146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.40
DANN	Benign	0.86
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism

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: rs4646698; hg19: chr3-125886441;