rs11000202

chr10-72173941-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001198800.3(ASCC1):c.490-12267T>C variant causes a intron change. The variant allele was found at a frequency of 0.38 in 152,122 control chromosomes in the GnomAD database, including 12,753 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (12753 hom., cov: 33)
• Consequence: ASCC1 NM_001198800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC1	NM_001198800.3	c.490-12267T>C		intron_variant		ENST00000672957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC1	ENST00000672957.1	c.490-12267T>C		intron_variant			NM_001198800.3	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57783 AN: 152004 Hom.: 12753 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.416

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.380 AC: 57792 AN: 152122 Hom.: 12753 Cov.: 33 AF XY: 0.371 AC XY: 27568 AN XY: 74390

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.410

Alfa AF: 0.489 Hom.: 21574

Bravo AF: 0.373

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	18
Dann	Benign	0.87

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

Other links and lift over

dbSNP: rs11000202; hg19: chr10-73933699;