Variant 12-102958393-C-CGCAGCAGCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004316.4(ASCL1):c.178_186dup(p.Gln60_Gln62dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 129 hom., cov: 0)

Exomes 𝑓: 0.017 ( 65 hom. )

Consequence

ASCL1
NM_004316.4 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.219

Variant links:

Genes affected

ASCL1 (HGNC:738): (achaete-scute family bHLH transcription factor 1) This gene encodes a member of the basic helix-loop-helix (BHLH) family of transcription factors. The protein activates transcription by binding to the E box (5'-CANNTG-3'). Dimerization with other BHLH proteins is required for efficient DNA binding. This protein plays a role in the neuronal commitment and differentiation and in the generation of olfactory and autonomic neurons. Mutations in this gene may contribute to the congenital central hypoventilation syndrome (CCHS) phenotype in rare cases. [provided by RefSeq, Jul 2008]

ASCL1 links:

PAH (HGNC:8582): (phenylalanine hydroxylase) This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine and is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017]

PAH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-102958393-C-CGCAGCAGCA is Benign according to our data. Variant chr12-102958393-C-CGCAGCAGCA is described in ClinVar as [Benign]. Clinvar id is 162757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCL1	NM_004316.4 linkuse as main transcript	c.178_186dup	p.Gln60_Gln62dup	inframe_insertion	1/2	ENST00000266744.4
PAH	NM_001354304.2 linkuse as main transcript	c.-295_-294insTGCTGCTGC		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ASCL1	ENST00000266744.4 linkuse as main transcript	c.178_186dup	p.Gln60_Gln62dup	inframe_insertion	1/2	1	NM_004316.4	P1
PAH	ENST00000547319.1 linkuse as main transcript	n.17_18insTGCTGCTGC		non_coding_transcript_exon_variant	1/3	4
PAH	ENST00000551337.5 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4297

AN:

150084

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0237

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.0483

Gnomad FIN

AF:

0.00295

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.00919

Gnomad OTH

AF:

0.0302

GnomAD4 exome

AF:

0.0166

AC:

22475

AN:

1356546

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

11411

AN XY:

669058

show subpopulations

Gnomad4 AFR exome

AF:

0.0518

Gnomad4 AMR exome

AF:

0.0243

Gnomad4 ASJ exome

AF:

0.0281

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.0397

Gnomad4 FIN exome

AF:

0.00349

Gnomad4 NFE exome

AF:

0.00872

Gnomad4 OTH exome

AF:

0.0251

GnomAD4 genome

AF:

0.0286

AC:

4294

AN:

150174

Hom.:

129

Cov.:

AF XY:

0.0296

AC XY:

2172

AN XY:

73306

show subpopulations

Gnomad4 AFR

AF:

0.0507

Gnomad4 AMR

AF:

0.0221

Gnomad4 ASJ

AF:

0.0237

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.0481

Gnomad4 FIN

AF:

0.00295

Gnomad4 NFE

AF:

0.00919

Gnomad4 OTH

AF:

0.0294

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 25, 2015	Gln51[15] in exon 1 of ASCL1: This variant is not expected to have clinical sign ificance because it has been reported in 19% (300/1604) of Japanese chromosomes (Ide 2005) and has been identified in 1.6% (5/304) of Caucasian control chromoso mes tested by our laboratory. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

This variant is associated with the following publications: (PMID: 14566559, 16021468, 20097173) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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