rs10934751

Variant names:

• chr3-126149670-A-G
• rs10934751
• NM_012190.4:c.984+736T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-126149670-A-G
• chr3-126149670-A-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.984+736T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,044 control chromosomes in the GnomAD database, including 14,047 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 0.42 (14047 hom., cov: 33)
• Consequence: ALDH1L1 NM_012190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	NM_012190.4	MANE Select	c.984+736T>C		intron	N/A	NP_036322.2
	ALDH1L1	NM_001270364.2		c.1014+736T>C		intron	N/A	NP_001257293.1	O75891-3
	ALDH1L1	NM_001270365.2		c.681+736T>C		intron	N/A	NP_001257294.1	O75891-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1L1	ENST00000393434.7	TSL:1 MANE Select	c.984+736T>C		intron	N/A	ENSP00000377083.3	O75891-1
	ALDH1L1	ENST00000273450.7	TSL:1	c.1014+736T>C		intron	N/A	ENSP00000273450.3	O75891-3
	ALDH1L1	ENST00000393431.6	TSL:1	c.984+736T>C		intron	N/A	ENSP00000377081.2	O75891-4

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64043 AN: 151926 Hom.: 14039 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.421 AC: 64076 AN: 152044 Hom.: 14047 Cov.: 33 AF XY: 0.418 AC XY: 31087 AN XY: 74312

African (AFR) AF: 0.305 AC: 12627 AN: 41466

American (AMR) AF: 0.447 AC: 6836 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3472

East Asian (EAS) AF: 0.577 AC: 2978 AN: 5160

South Asian (SAS) AF: 0.395 AC: 1906 AN: 4820

European-Finnish (FIN) AF: 0.369 AC: 3897 AN: 10568

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32538 AN: 67954

Other (OTH) AF: 0.469 AC: 991 AN: 2112

Alfa AF: 0.466 Hom.: 63859

Bravo AF: 0.421

Asia WGS AF: 0.507 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.42
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: rs10934751; hg19: chr3-125868513;