rs146370051

Positions:

chr10-72133059-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001198800.3(ASCC1):c.869A>G(p.Asn290Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,613,978 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 3 hom. )

Consequence

ASCC1
NM_001198800.3 missense, splice_region

Scores

Splicing: ADA: 0.00006728

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 0.926

Variant links:

Genes affected

ASCC1 (HGNC:24268): (activating signal cointegrator 1 complex subunit 1) This gene encodes a subunit of the activating signal cointegrator 1 (ASC-1) complex. The ASC-1 complex is a transcriptional coactivator that plays an important role in gene transactivation by multiple transcription factors including activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). The encoded protein contains an N-terminal KH-type RNA-binding motif which is required for AP-1 transactivation by the ASC-1 complex. Mutations in this gene are associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ASCC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004810542).

BP6

Variant 10-72133059-T-C is Benign according to our data. Variant chr10-72133059-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 31129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-72133059-T-C is described in Lovd as [Likely_pathogenic].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00128 (195/152296) while in subpopulation NFE AF= 0.00229 (156/68016). AF 95% confidence interval is 0.002. There are 0 homozygotes in gnomad4. There are 84 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 195 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC1	NM_001198800.3 linkuse as main transcript	c.869A>G	p.Asn290Ser	missense_variant, splice_region_variant	8/10	ENST00000672957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC1	ENST00000672957.1 linkuse as main transcript	c.869A>G	p.Asn290Ser	missense_variant, splice_region_variant	8/10		NM_001198800.3	P1	Q8N9N2-2

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00117

AC:

294

AN:

251444

Hom.:

AF XY:

0.00131

AC XY:

178

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00209

AC:

3052

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1493

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00248

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152296

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00129

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00117

AC:

142

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00202

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 11, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	ASCC1: BP4 -

Barrett esophagus/esophageal adenocarcinoma

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 27, 2011

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Aug 07, 2018

- -

Spinal muscular atrophy with congenital bone fractures 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.82

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.79

T;.;.;.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0048

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

0.70

N;N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.37

N;N;N;N;N

REVEL

Benign

0.030

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0030

.;B;.;.;B

Vest4

0.12

MVP

0.19

MPC

0.14

ClinPred

0.011

GERP RS

2.1

Varity_R

0.042

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000067

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.020

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