rs731682

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004316.4(ASCL1):c.627C>G(p.Val209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 1,613,968 control chromosomes in the GnomAD database, including 3,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 1043 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2664 hom. )

Consequence

ASCL1
NM_004316.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 12-102958871-C-G is Benign according to our data. Variant chr12-102958871-C-G is described in ClinVar as [Benign]. Clinvar id is 162758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 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.627C>G	p.Val209=	synonymous_variant	1/2	ENST00000266744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCL1	ENST00000266744.4 linkuse as main transcript	c.627C>G	p.Val209=	synonymous_variant	1/2	1	NM_004316.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0870

AC:

13237

AN:

152204

Hom.:

1037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0349

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0225

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0512

Gnomad OTH

AF:

0.0694

GnomAD3 exomes

AF:

0.0491

AC:

12147

AN:

247292

Hom.:

610

AF XY:

0.0462

AC XY:

6230

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.0256

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.0225

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0514

Gnomad OTH exome

AF:

0.0413

GnomAD4 exome

AF:

0.0524

AC:

76621

AN:

1461646

Hom.:

2664

Cov.:

AF XY:

0.0513

AC XY:

37338

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.0273

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0243

Gnomad4 FIN exome

AF:

0.0201

Gnomad4 NFE exome

AF:

0.0532

Gnomad4 OTH exome

AF:

0.0518

GnomAD4 genome

AF:

0.0871

AC:

13262

AN:

152322

Hom.:

1043

Cov.:

AF XY:

0.0837

AC XY:

6234

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.0349

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.0174

Gnomad4 NFE

AF:

0.0512

Gnomad4 OTH

AF:

0.0682

Alfa

AF:

0.0654

Hom.:

134

Bravo

AF:

0.0954

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0509

EpiControl

AF:

0.0546

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Val209Val in exon 1 of ASCL1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 20.1% (887/4402) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs731682). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

Cadd

Benign

9.9

Dann

Benign

0.84

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

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