Variant 10-95611185-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002860.4(ALDH18A1):c.2110+71C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,573,114 control chromosomes in the GnomAD database, including 12,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1031 hom., cov: 33)

Exomes 𝑓: 0.13 ( 11814 hom. )

Consequence

ALDH18A1
NM_002860.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.251

Variant links:

Genes affected

ALDH18A1 (HGNC:9722): (aldehyde dehydrogenase 18 family member A1) This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]

ALDH18A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-95611185-G-C is Benign according to our data. Variant chr10-95611185-G-C is described in ClinVar as [Benign]. Clinvar id is 1242768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH18A1	NM_002860.4 linkuse as main transcript	c.2110+71C>G		intron_variant		ENST00000371224.7	NP_002851.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH18A1	ENST00000371224.7 linkuse as main transcript	c.2110+71C>G		intron_variant		1	NM_002860.4	ENSP00000360268	P3	P54886-1
ALDH18A1	ENST00000371221.3 linkuse as main transcript	c.2104+71C>G		intron_variant		1		ENSP00000360265	A1	P54886-2

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16141

AN:

152114

Hom.:

1031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0491

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.0408

Gnomad SAS

AF:

0.0731

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.130

GnomAD4 exome

AF:

0.126

AC:

178576

AN:

1420882

Hom.:

11814

AF XY:

0.125

AC XY:

88721

AN XY:

708410

show subpopulations

Gnomad4 AFR exome

AF:

0.0447

Gnomad4 AMR exome

AF:

0.0753

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.0374

Gnomad4 SAS exome

AF:

0.0796

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.106

AC:

16136

AN:

152232

Hom.:

1031

Cov.:

AF XY:

0.105

AC XY:

7843

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0490

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.0411

Gnomad4 SAS

AF:

0.0732

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.0417

Hom.:

Bravo

AF:

0.101

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	GeneDx	Jun 26, 2018	- -
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

-0.83

CADD

Benign

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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