rs6594713

Positions:

• chr5-113379677-A-C
• chr5-113379677-A-G

Variant summary

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

The NM_001085377.2(MCC):​c.415+5291T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,200 control chromosomes in the GnomAD database, including 2,470 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 0.17 (2470 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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]

ENSG00000232633 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCC	NM_001085377.2	c.415+5291T>G		intron_variant		ENST00000408903.7	NP_001078846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.415+5291T>G		intron_variant		2	NM_001085377.2	ENSP00000386227.3
ENSG00000232633	ENST00000416046.2	n.247-20266A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26195 AN: 152082 Hom.: 2468 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.172 AC: 26208 AN: 152200 Hom.: 2470 Cov.: 32 AF XY: 0.168 AC XY: 12484 AN XY: 74394

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0894

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.165

Alfa AF: 0.121 Hom.: 211

Bravo AF: 0.168

Asia WGS AF: 0.0980 AC: 340 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.47

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: rs6594713; hg19: chr5-112715374;