rs397768

Variant names:

• chr5-112845879-G-A
• rs397768
• NM_000038.6:c.*1753G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-112845879-G-A
• chr5-112845879-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000038.6(APC):​c.*1753G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 231,790 control chromosomes in the GnomAD database, including 48,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (30503 hom., cov: 31)
  • Exomes 𝑓: 0.66 (17602 hom.)
• Consequence: APC NM_000038.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.210

Genes affected

APC (HGNC:583): (APC regulator of WNT signaling pathway) This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Mutations in the APC gene have been found to occur in most colorectal cancers, where disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. [provided by RefSeq, Jun 2022]

ENSG00000258864 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-112845879-G-A is Benign according to our data. Variant chr5-112845879-G-A is described in ClinVar as [Benign]. Clinvar id is 83263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6	c.*1753G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000257430.9	NP_000029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9	c.*1753G>A		3_prime_UTR_variant	Exon 16 of 16	5	NM_000038.6	ENSP00000257430.4
ENSG00000258864	ENST00000520401.1	n.229-10770G>A		intron_variant	Intron 3 of 7	3		ENSP00000454861.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95738 AN: 151804 Hom.: 30487 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.640

GnomAD4 exome AF: 0.660 AC: 52686 AN: 79868 Hom.: 17602 Cov.: 0 AF XY: 0.658 AC XY: 24159 AN XY: 36720

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.606

Gnomad4 EAS exome AF: 0.848

Gnomad4 SAS exome AF: 0.732

Gnomad4 FIN exome AF: 0.518

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.631 AC: 95809 AN: 151922 Hom.: 30503 Cov.: 31 AF XY: 0.632 AC XY: 46922 AN XY: 74234

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.637

Alfa AF: 0.616 Hom.: 4101

Bravo AF: 0.643

Asia WGS AF: 0.760 AC: 2635 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

APC-Associated Polyposis Disorders Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Familial colorectal cancer Other:1

-

Systems Biology Platform Zhejiang California International NanoSystems Institute

Significance: other

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs397768; hg19: chr5-112181576; COSMIC: COSV57321672; COSMIC: COSV57321672;