rs414098

Variant names:

• chr5-112778075-G-A
• rs414098
• NM_000038.6:c.531+2338G>A

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+2338G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 207,008 control chromosomes in the GnomAD database, including 21,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (14775 hom., cov: 33)
  • Exomes 𝑓: 0.50 (7217 hom.)
• Consequence: APC NM_000038.6 intron
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 3.10
• Publications: 6 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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+2338G>A		intron	N/A	NP_000029.2
	APC	NM_001407446.1		c.561+2338G>A		intron	N/A	NP_001394375.1
	APC	NM_001354896.2		c.531+2338G>A		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+2338G>A		intron	N/A	ENSP00000257430.4	P25054-1
	APC	ENST00000508376.6	TSL:1	c.531+2338G>A		intron	N/A	ENSP00000427089.2	P25054-1
	APC	ENST00000502371.3	TSL:1	n.531+2338G>A		intron	N/A	ENSP00000484935.2	A0A087X2F3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61028 AN: 151656 Hom.: 14777 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.497 AC: 27460 AN: 55234 Hom.: 7217 Cov.: 0 AF XY: 0.486 AC XY: 15810 AN XY: 32538

African (AFR) AF: 0.103 AC: 161 AN: 1560

American (AMR) AF: 0.680 AC: 4882 AN: 7182

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 396 AN: 822

East Asian (EAS) AF: 0.664 AC: 1930 AN: 2906

South Asian (SAS) AF: 0.489 AC: 2840 AN: 5806

European-Finnish (FIN) AF: 0.422 AC: 3120 AN: 7392

Middle Eastern (MID) AF: 0.543 AC: 38 AN: 70

European-Non Finnish (NFE) AF: 0.477 AC: 13102 AN: 27454

Other (OTH) AF: 0.485 AC: 991 AN: 2042

GnomAD4 genome AF: 0.402 AC: 61029 AN: 151774 Hom.: 14775 Cov.: 33 AF XY: 0.405 AC XY: 30059 AN XY: 74162

African (AFR) AF: 0.127 AC: 5271 AN: 41468

American (AMR) AF: 0.569 AC: 8666 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1659 AN: 3458

East Asian (EAS) AF: 0.664 AC: 3423 AN: 5152

South Asian (SAS) AF: 0.550 AC: 2653 AN: 4824

European-Finnish (FIN) AF: 0.414 AC: 4348 AN: 10514

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33495 AN: 67824

Other (OTH) AF: 0.441 AC: 931 AN: 2110

Alfa AF: 0.415 Hom.: 1928

Bravo AF: 0.406

Asia WGS AF: 0.563 AC: 1956 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	-0.72
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		3.1
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: rs414098; hg19: chr5-112113772;