10-72097226-A-G

Variant names:

• chr10-72097226-A-G
• rs3312
• NM_001198800.3:c.*108T>C

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.*108T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 816,300 control chromosomes in the GnomAD database, including 91,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19382 hom., cov: 32)
  • Exomes 𝑓: 0.46 (71758 hom.)
• Consequence: ASCC1 NM_001198800.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.103
• Publications: 20 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: Illumina, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-72097226-A-G is Benign according to our data. Variant chr10-72097226-A-G is described in ClinVar as Benign. ClinVar VariationId is 1262551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 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.*108T>C		3_prime_UTR	Exon 10 of 10	NP_001185729.1	Q8N9N2-2
	ASCC1	NM_001198799.3		c.*260T>C		3_prime_UTR	Exon 13 of 13	NP_001185728.1	Q8N9N2-1
	ASCC1	NM_001369085.1		c.*260T>C		3_prime_UTR	Exon 12 of 12	NP_001356014.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	ENST00000672957.1	MANE Select	c.*108T>C		3_prime_UTR	Exon 10 of 10	ENSP00000500935.1	Q8N9N2-2
	ASCC1	ENST00000342444.8	TSL:2	c.*260T>C		3_prime_UTR	Exon 13 of 13	ENSP00000339404.4	Q8N9N2-1
	ASCC1	ENST00000902262.1		c.*108T>C		3_prime_UTR	Exon 11 of 11	ENSP00000572321.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75199 AN: 151920 Hom.: 19348 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.497

GnomAD2 exomes AF: 0.453 AC: 112790 AN: 249026 AF XY: 0.459

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.293

Gnomad FIN exome AF: 0.391

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.459 AC: 304663 AN: 664262 Hom.: 71758 Cov.: 9 AF XY: 0.465 AC XY: 166745 AN XY: 358822

African (AFR) AF: 0.622 AC: 11201 AN: 18008

American (AMR) AF: 0.385 AC: 16447 AN: 42670

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 8506 AN: 20190

East Asian (EAS) AF: 0.302 AC: 10247 AN: 33972

South Asian (SAS) AF: 0.535 AC: 37480 AN: 70046

European-Finnish (FIN) AF: 0.397 AC: 19395 AN: 48826

Middle Eastern (MID) AF: 0.554 AC: 2301 AN: 4152

European-Non Finnish (NFE) AF: 0.467 AC: 183609 AN: 393356

Other (OTH) AF: 0.468 AC: 15477 AN: 33042

GnomAD4 genome AF: 0.495 AC: 75280 AN: 152038 Hom.: 19382 Cov.: 32 AF XY: 0.486 AC XY: 36155 AN XY: 74338

African (AFR) AF: 0.625 AC: 25907 AN: 41444

American (AMR) AF: 0.431 AC: 6580 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1419 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1504 AN: 5172

South Asian (SAS) AF: 0.522 AC: 2517 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3891 AN: 10564

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31858 AN: 67972

Other (OTH) AF: 0.496 AC: 1045 AN: 2108

Alfa AF: 0.473 Hom.: 68919

Bravo AF: 0.501

Asia WGS AF: 0.438 AC: 1520 AN: 3478

ClinVar

ClinVar submissions

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	-0.76
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3312; hg19: chr10-73856984; COSMIC: COSV57725205; COSMIC: COSV57725205;