NM_001198800.3:c.958-4824G>A

Variant names:

• chr10-72102274-C-T
• rs1668154
• NM_001198800.3:c.958-4824G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.137
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• spinal muscular atrophy with congenital bone fractures 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1289137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198800.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	NM_001198800.3	MANE Select	c.958-4824G>A		intron	N/A	NP_001185729.1
	ASCC1	NM_001198799.3		c.*35+60G>A		intron	N/A	NP_001185728.1
	ASCC1	NM_001369085.1		c.*35+60G>A		intron	N/A	NP_001356014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	ENST00000672957.1	MANE Select	c.958-4824G>A		intron	N/A	ENSP00000500935.1
	ASCC1	ENST00000342444.8	TSL:2	c.*35+60G>A		intron	N/A	ENSP00000339404.4
	ASCC1	ENST00000902262.1		c.1042-4824G>A		intron	N/A	ENSP00000572321.1

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

African (AFR) AF: 0.208 AC: 6016 AN: 28908

American (AMR) AF: 0.341 AC: 12011 AN: 35208

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 10287 AN: 24220

East Asian (EAS) AF: 0.172 AC: 5978 AN: 34730

South Asian (SAS) AF: 0.450 AC: 34453 AN: 76572

European-Finnish (FIN) AF: 0.357 AC: 16671 AN: 46700

Middle Eastern (MID) AF: 0.487 AC: 2672 AN: 5484

European-Non Finnish (NFE) AF: 0.435 AC: 425854 AN: 979628

Other (OTH) AF: 0.402 AC: 21738 AN: 54008

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

African (AFR) AF: 0.216 AC: 8940 AN: 41404

American (AMR) AF: 0.356 AC: 5441 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1448 AN: 3470

East Asian (EAS) AF: 0.136 AC: 704 AN: 5184

South Asian (SAS) AF: 0.434 AC: 2094 AN: 4820

European-Finnish (FIN) AF: 0.324 AC: 3423 AN: 10562

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.433 AC: 29430 AN: 67954

Other (OTH) AF: 0.376 AC: 791 AN: 2106

Alfa AF: 0.397 Hom.: 30542

Bravo AF: 0.341

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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