rs11000190

Variant names:

• chr10-72148450-A-G
• rs11000190
• NM_001198800.3:c.746+4419T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001198800.3(ASCC1):​c.746+4419T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,182 control chromosomes in the GnomAD database, including 5,997 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 0.16 (5997 hom., cov: 32)
• Consequence: ASCC1 NM_001198800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	NM_001198800.3	MANE Select	c.746+4419T>C		intron	N/A	NP_001185729.1
	ASCC1	NM_001198799.3		c.830+4419T>C		intron	N/A	NP_001185728.1
	ASCC1	NM_001369085.1		c.812+4419T>C		intron	N/A	NP_001356014.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	ENST00000672957.1	MANE Select	c.746+4419T>C		intron	N/A	ENSP00000500935.1
	ASCC1	ENST00000342444.8	TSL:2	c.830+4419T>C		intron	N/A	ENSP00000339404.4
	ASCC1	ENST00000394915.7	TSL:5	c.830+4419T>C		intron	N/A	ENSP00000378373.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23914 AN: 152064 Hom.: 5972 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.158 AC: 23986 AN: 152182 Hom.: 5997 Cov.: 32 AF XY: 0.153 AC XY: 11412 AN XY: 74432

African (AFR) AF: 0.529 AC: 21934 AN: 41438

American (AMR) AF: 0.0572 AC: 875 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.0968 AC: 502 AN: 5186

South Asian (SAS) AF: 0.0387 AC: 187 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00315 AC: 214 AN: 68022

Other (OTH) AF: 0.114 AC: 241 AN: 2108

Alfa AF: 0.0490 Hom.: 807

Bravo AF: 0.178

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.4
DANN	Benign	0.85
PhyloP100		-0.10
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: rs11000190; hg19: chr10-73908208;