rs76028897

Positions:

• chr5-112716300-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001407446.1(APC):​c.165+8418A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 152,148 control chromosomes in the GnomAD database, including 337 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 0.049 (337 hom., cov: 32)
• Consequence: APC NM_001407446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_001407446.1	c.165+8418A>G		intron_variant			NP_001394375.1
APC	NM_001407447.1	c.-19+8418A>G		intron_variant			NP_001394376.1
APC	NM_001407448.1	c.-19+8651A>G		intron_variant			NP_001394377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000509732.6	c.-19+8651A>G		intron_variant		4		ENSP00000426541.2
APC	ENST00000507379.6	c.165+8418A>G		intron_variant		2		ENSP00000423224.2
APC	ENST00000505350.2	n.165+8418A>G		intron_variant		3		ENSP00000481752.1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7490 AN: 152030 Hom.: 337 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.00595

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0618

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

GnomAD4 genome AF: 0.0493 AC: 7494 AN: 152148 Hom.: 337 Cov.: 32 AF XY: 0.0496 AC XY: 3686 AN XY: 74382

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0264

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0678

Gnomad4 FIN AF: 0.00595

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0345 Hom.: 21

Bravo AF: 0.0544

Asia WGS AF: 0.110 AC: 380 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.4
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76028897; hg19: chr5-112051997;