Variant 3-126107135-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012190.4(ALDH1L1):c.2453+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 1,613,134 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 82 hom. )

Consequence

ALDH1L1
NM_012190.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.00008391

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0150

Variant links:

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 links:

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

ALDH1L1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 3-126107135-C-T is Benign according to our data. Variant chr3-126107135-C-T is described in ClinVar as [Benign]. Clinvar id is 713087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-126107135-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1L1	NM_012190.4 linkuse as main transcript	c.2453+6G>A		splice_donor_region_variant, intron_variant		ENST00000393434.7	NP_036322.2
ALDH1L1-AS1	NR_046602.1 linkuse as main transcript	n.252-749C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1L1	ENST00000393434.7 linkuse as main transcript	c.2453+6G>A		splice_donor_region_variant, intron_variant		1	NM_012190.4	ENSP00000377083	P1	O75891-1
ALDH1L1-AS1	ENST00000512384.1 linkuse as main transcript	n.252-749C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00773

AC:

1177

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0318

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00811

AC:

2038

AN:

251392

Hom.:

AF XY:

0.00825

AC XY:

1121

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.0307

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00880

GnomAD4 exome

AF:

0.00733

AC:

10713

AN:

1460782

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

5343

AN XY:

726726

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000847

Gnomad4 FIN exome

AF:

0.0309

Gnomad4 NFE exome

AF:

0.00755

Gnomad4 OTH exome

AF:

0.00687

GnomAD4 genome

AF:

0.00773

AC:

1177

AN:

152352

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

663

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00313

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0318

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00932

Hom.:

Bravo

AF:

0.00467

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00763

EpiControl

AF:

0.00599

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000084

dbscSNV1_RF

Benign

0.074

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over