rs1395970563

Positions:

• chr5-112707716-C-A
• chr5-112707716-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001407446.1(APC):​c.-2C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000821 in 1,218,368 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: APC NM_001407446.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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]

APC (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_001407446.1	c.-2C>A		5_prime_UTR_variant	1/16		NP_001394375.1
APC	NM_001407447.1	c.-185C>A		5_prime_UTR_variant	1/17		NP_001394376.1
APC	NM_001354897.2	c.-2C>A		5_prime_UTR_variant	1/15		NP_001341826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000507379	c.-2C>A		5_prime_UTR_variant	1/14	2		ENSP00000423224.2
APC	ENST00000509732.6	c.-19+67C>A		intron_variant		4		ENSP00000426541.2
APC	ENST00000505350.2	n.-2C>A		non_coding_transcript_exon_variant	1/16	3		ENSP00000481752.1
APC	ENST00000505350.2	n.-2C>A		5_prime_UTR_variant	1/16	3		ENSP00000481752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.21e-7 AC: 1 AN: 1218368 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 595220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000103

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.86

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-112043413;