NM_001198800.3:c.489+917G>C

Variant names:

• chr10-72195894-C-G
• rs11000212
• NM_001198800.3:c.489+917G>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.489+917G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,664 control chromosomes in the GnomAD database, including 27,347 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 0.58 (27347 hom., cov: 31)
• Consequence: ASCC1 NM_001198800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC1	NM_001198800.3	c.489+917G>C		intron_variant	Intron 5 of 9	ENST00000672957.1	NP_001185729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC1	ENST00000672957.1	c.489+917G>C		intron_variant	Intron 5 of 9		NM_001198800.3	ENSP00000500935.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87780 AN: 151552 Hom.: 27295 Cov.: 31

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.579 AC: 87875 AN: 151664 Hom.: 27347 Cov.: 31 AF XY: 0.565 AC XY: 41799 AN XY: 74044

African (AFR) AF: 0.805 AC: 33354 AN: 41438

American (AMR) AF: 0.478 AC: 7277 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3466

East Asian (EAS) AF: 0.248 AC: 1279 AN: 5162

South Asian (SAS) AF: 0.514 AC: 2471 AN: 4808

European-Finnish (FIN) AF: 0.362 AC: 3752 AN: 10364

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36133 AN: 67904

Other (OTH) AF: 0.563 AC: 1182 AN: 2100

Alfa AF: 0.393 Hom.: 948

Bravo AF: 0.594

Asia WGS AF: 0.389 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.31
PhyloP100		-1.7
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: rs11000212; hg19: chr10-73955652;