5-112777830-A-T

Variant names:

• chr5-112777830-A-T
• rs467033
• NM_000038.6:c.531+2093A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000038.6(APC):​c.531+2093A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 243,976 control chromosomes in the GnomAD database, including 26,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.41 (15243 hom., cov: 32)
  • Exomes 𝑓: 0.48 (11252 hom.)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 0.950
• Publications: 9 publications found

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]

CBX3P3 (HGNC:42875): (CBX3 pseudogene 3)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000038.6. 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
	APC	NM_000038.6	MANE Select	c.531+2093A>T		intron	N/A	NP_000029.2
	APC	NM_001407446.1		c.561+2093A>T		intron	N/A	NP_001394375.1
	APC	NM_001354896.2		c.531+2093A>T		intron	N/A	NP_001341825.1	R4GMU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APC	ENST00000257430.9	TSL:5 MANE Select	c.531+2093A>T		intron	N/A	ENSP00000257430.4	P25054-1
	APC	ENST00000508376.6	TSL:1	c.531+2093A>T		intron	N/A	ENSP00000427089.2	P25054-1
	APC	ENST00000502371.3	TSL:1	n.531+2093A>T		intron	N/A	ENSP00000484935.2	A0A087X2F3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62014 AN: 151922 Hom.: 15247 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.478 AC: 43955 AN: 91936 Hom.: 11252 Cov.: 0 AF XY: 0.469 AC XY: 25778 AN XY: 55008

African (AFR) AF: 0.115 AC: 246 AN: 2136

American (AMR) AF: 0.695 AC: 6023 AN: 8672

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 649 AN: 1404

East Asian (EAS) AF: 0.682 AC: 2792 AN: 4096

South Asian (SAS) AF: 0.490 AC: 4481 AN: 9146

European-Finnish (FIN) AF: 0.426 AC: 6664 AN: 15660

Middle Eastern (MID) AF: 0.440 AC: 251 AN: 570

European-Non Finnish (NFE) AF: 0.454 AC: 21266 AN: 46806

Other (OTH) AF: 0.459 AC: 1583 AN: 3446

GnomAD4 genome AF: 0.408 AC: 62014 AN: 152040 Hom.: 15243 Cov.: 32 AF XY: 0.411 AC XY: 30544 AN XY: 74300

African (AFR) AF: 0.129 AC: 5339 AN: 41518

American (AMR) AF: 0.577 AC: 8819 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1782 AN: 3466

East Asian (EAS) AF: 0.656 AC: 3382 AN: 5152

South Asian (SAS) AF: 0.551 AC: 2660 AN: 4824

European-Finnish (FIN) AF: 0.415 AC: 4371 AN: 10544

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34116 AN: 67930

Other (OTH) AF: 0.447 AC: 944 AN: 2112

Alfa AF: 0.296 Hom.: 798

Bravo AF: 0.411

Asia WGS AF: 0.568 AC: 1971 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: other

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Familial colorectal cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.2
DANN	Benign	0.69
PhyloP100		0.95
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: rs467033; hg19: chr5-112113527;