10-72102274-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001198800.3(ASCC1):c.958-4824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,437,430 control chromosomes in the GnomAD database, including 124,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (10031 hom., cov: 32)
  • Exomes 𝑓: 0.42 (114707 hom.)
• Consequence: ASCC1 NM_001198800.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.137

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 10-72102274-C-T is Benign according to our data. Variant chr10-72102274-C-T is described in ClinVar as [Benign]. Clinvar id is 1289137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC1	NM_001198800.3	c.958-4824G>A		intron_variant		ENST00000672957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC1	ENST00000672957.1	c.958-4824G>A		intron_variant			NM_001198800.3	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52831 AN: 151854 Hom.: 10030 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.417 AC: 535680 AN: 1285458 Hom.: 114707 AF XY: 0.420 AC XY: 268492 AN XY: 639380

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.348 AC: 52839 AN: 151972 Hom.: 10031 Cov.: 32 AF XY: 0.342 AC XY: 25430 AN XY: 74276

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.376

Alfa AF: 0.411 Hom.: 19743

Bravo AF: 0.341

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	6.9
Dann	Benign	0.80

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: rs1668154; hg19: chr10-73862032; COSMIC: COSV57729984; COSMIC: COSV57729984;