rs879253781

Positions:

• chr5-112707592-GA-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001407446.1(APC):​c.-125del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: APC NM_001407446.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_001127511.3	c.-125del		5_prime_UTR_variant	1/14		NP_001120983.2
APC	NM_001354895.2	c.-308del		5_prime_UTR_variant	1/16		NP_001341824.1
APC	NM_001354897.2	c.-125del		5_prime_UTR_variant	1/15		NP_001341826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000507379.6	c.-125del		5_prime_UTR_variant	1/14	2		ENSP00000423224
APC	ENST00000509732.6	c.-75del		5_prime_UTR_variant	1/16	4		ENSP00000426541	P1
APC	ENST00000505350.2	c.-125del		5_prime_UTR_variant, NMD_transcript_variant	1/16	3		ENSP00000481752

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879253781; hg19: chr5-112043289;