rs10068491

Variant names:

• chr5-113150478-A-G
• rs10068491
• NM_001085377.2:c.741+831T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085377.2. 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
	MCC	NM_001085377.2	MANE Select	c.741+831T>C		intron	N/A	NP_001078846.2
	MCC	NM_002387.3		c.171+831T>C		intron	N/A	NP_002378.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCC	ENST00000408903.7	TSL:2 MANE Select	c.741+831T>C		intron	N/A	ENSP00000386227.3
	MCC	ENST00000302475.9	TSL:1	c.171+831T>C		intron	N/A	ENSP00000305617.4
	MCC	ENST00000515367.6	TSL:5	c.-19+831T>C		intron	N/A	ENSP00000421615.2

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

African (AFR) AF: 0.250 AC: 10362 AN: 41452

American (AMR) AF: 0.295 AC: 4500 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3468

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5160

South Asian (SAS) AF: 0.377 AC: 1815 AN: 4810

European-Finnish (FIN) AF: 0.388 AC: 4085 AN: 10524

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19945 AN: 67950

Other (OTH) AF: 0.282 AC: 594 AN: 2110

Alfa AF: 0.290 Hom.: 24410

Bravo AF: 0.277

Asia WGS AF: 0.293 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		0.58
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: rs10068491; hg19: chr5-112486175;