10-72102392-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001198800.3(ASCC1):c.958-4942C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,549,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASCC1 NM_001198800.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.484

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09204227).
• BP6: Variant 10-72102392-G-C is Benign according to our data. Variant chr10-72102392-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2917740.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC1	NM_001198800.3	c.958-4942C>G		intron_variant		ENST00000672957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC1	ENST00000672957.1	c.958-4942C>G		intron_variant			NM_001198800.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151722 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398140 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689590

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151722 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74136

Gnomad4 AFR AF: 0.0000732

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	3.3
Dann	Benign	0.92
DEOGEN2	Benign	0.0023	T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.045	N
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.99	L;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.052
Sift	Benign	0.048	D;D
Sift4G	Benign	0.070	T;T
Polyphen		0.61	P;P
Vest4		0.21
MVP		0.23
MPC		0.18
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1022983752; hg19: chr10-73862150;