10-72097226-A-G

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.*108T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 816,300 control chromosomes in the GnomAD database, including 91,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19382 hom., cov: 32)
  • Exomes 𝑓: 0.46 (71758 hom.)
• Consequence: ASCC1 NM_001198800.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103

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=-0.76).
• BP6: Variant 10-72097226-A-G is Benign according to our data. Variant chr10-72097226-A-G is described in ClinVar as [Benign]. Clinvar id is 1262551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC1	NM_001198800.3	c.*108T>C		3_prime_UTR_variant	10/10	ENST00000672957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC1	ENST00000672957.1	c.*108T>C		3_prime_UTR_variant	10/10		NM_001198800.3	P1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75199 AN: 151920 Hom.: 19348 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.497

GnomAD3 exomes AF: 0.453 AC: 112790 AN: 249026 Hom.: 26510 AF XY: 0.459 AC XY: 61862 AN XY: 134818

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.293

Gnomad SAS exome AF: 0.535

Gnomad FIN exome AF: 0.391

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.459 AC: 304663 AN: 664262 Hom.: 71758 Cov.: 9 AF XY: 0.465 AC XY: 166745 AN XY: 358822

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.468

GnomAD4 genome AF: 0.495 AC: 75280 AN: 152038 Hom.: 19382 Cov.: 32 AF XY: 0.486 AC XY: 36155 AN XY: 74338

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.496

Alfa AF: 0.468 Hom.: 30316

Bravo AF: 0.501

Asia WGS AF: 0.438 AC: 1520 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	6.7
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3312; hg19: chr10-73856984; COSMIC: COSV57725205; COSMIC: COSV57725205;