10-72173941-A-G

Variant names:

• chr10-72173941-A-G
• rs11000202
• NM_001198800.3:c.490-12267T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001198800.3(ASCC1):​c.490-12267T>C variant causes a intron change. The variant allele was found at a frequency of 0.38 in 152,122 control chromosomes in the GnomAD database, including 12,753 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 0.38 (12753 hom., cov: 33)
• Consequence: ASCC1 NM_001198800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 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.490-12267T>C		intron	N/A	NP_001185729.1
	ASCC1	NM_001198799.3		c.574-12267T>C		intron	N/A	NP_001185728.1
	ASCC1	NM_001369085.1		c.556-12267T>C		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.490-12267T>C		intron	N/A	ENSP00000500935.1
	ASCC1	ENST00000342444.8	TSL:2	c.574-12267T>C		intron	N/A	ENSP00000339404.4
	ASCC1	ENST00000394915.7	TSL:5	c.574-12267T>C		intron	N/A	ENSP00000378373.3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57783 AN: 152004 Hom.: 12753 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.380 AC: 57792 AN: 152122 Hom.: 12753 Cov.: 33 AF XY: 0.371 AC XY: 27568 AN XY: 74390

African (AFR) AF: 0.176 AC: 7287 AN: 41500

American (AMR) AF: 0.397 AC: 6065 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3470

East Asian (EAS) AF: 0.138 AC: 716 AN: 5182

South Asian (SAS) AF: 0.448 AC: 2158 AN: 4822

European-Finnish (FIN) AF: 0.351 AC: 3719 AN: 10584

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34739 AN: 67962

Other (OTH) AF: 0.410 AC: 866 AN: 2110

Alfa AF: 0.478 Hom.: 25942

Bravo AF: 0.373

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.87
PhyloP100		4.1
Mutation Taster		=98/2	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: rs11000202; hg19: chr10-73933699;