rs13174818

Positions:

• chr5-113077782-C-T

Variant summary

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

The NM_001085377.2(MCC):​c.1784+5078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,872 control chromosomes in the GnomAD database, including 22,588 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 0.51 (22588 hom., cov: 31)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

Genes affected

MCC (HGNC:6935): (MCC regulator of WNT signaling pathway) This gene is a candidate colorectal tumor suppressor gene that is thought to negatively regulate cell cycle progression. The orthologous gene in the mouse expresses a phosphoprotein associated with the plasma membrane and membrane organelles, and overexpression of the mouse protein inhibits entry into S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCC	NM_001085377.2	c.1784+5078G>A		intron_variant		ENST00000408903.7
MCC	NM_002387.3	c.1214+5078G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCC	ENST00000408903.7	c.1784+5078G>A		intron_variant		2	NM_001085377.2	P1
MCC	ENST00000302475.9	c.1214+5078G>A		intron_variant		1
MCC	ENST00000514701.5	c.1214+5078G>A		intron_variant		2
MCC	ENST00000515367.6	c.1025+5078G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77449 AN: 151754 Hom.: 22582 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.510 AC: 77468 AN: 151872 Hom.: 22588 Cov.: 31 AF XY: 0.513 AC XY: 38105 AN XY: 74228

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.556

Alfa AF: 0.550 Hom.: 3095

Bravo AF: 0.502

Asia WGS AF: 0.566 AC: 1967 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.7
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs13174818; hg19: chr5-112413479;