rs10068491

Positions:

• chr5-113150478-A-G
• chr5-113150478-A-T

Variant summary

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

The NM_001085377.2(MCC):​c.741+831T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,954 control chromosomes in the GnomAD database, including 6,473 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 0.29 (6473 hom., cov: 31)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCC	NM_001085377.2	c.741+831T>C		intron_variant		ENST00000408903.7
MCC	NM_002387.3	c.171+831T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCC	ENST00000408903.7	c.741+831T>C		intron_variant		2	NM_001085377.2	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43766 AN: 151836 Hom.: 6473 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.288 AC: 43783 AN: 151954 Hom.: 6473 Cov.: 31 AF XY: 0.295 AC XY: 21909 AN XY: 74254

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.282

Alfa AF: 0.290 Hom.: 10748

Bravo AF: 0.277

Asia WGS AF: 0.293 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.91

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: rs10068491; hg19: chr5-112486175;