5-113402923-C-G

Variant names:

• chr5-113402923-C-G
• rs6594714
• NM_001085377.2:c.171-17711G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085377.2(MCC):​c.171-17711G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,000 control chromosomes in the GnomAD database, including 2,450 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 (2450 hom., cov: 31)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 0 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]

ENSG00000232633 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.171-17711G>C		intron_variant	Intron 1 of 18	ENST00000408903.7	NP_001078846.2
LOC107986366	XR_001742459.2	n.59+2924C>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.171-17711G>C		intron_variant	Intron 1 of 18	2	NM_001085377.2	ENSP00000386227.3
ENSG00000232633	ENST00000416046.3	n.303+2924C>G		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26032 AN: 151882 Hom.: 2448 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.171 AC: 26041 AN: 152000 Hom.: 2450 Cov.: 31 AF XY: 0.167 AC XY: 12414 AN XY: 74286

African (AFR) AF: 0.118 AC: 4899 AN: 41474

American (AMR) AF: 0.142 AC: 2171 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3466

East Asian (EAS) AF: 0.0894 AC: 460 AN: 5146

South Asian (SAS) AF: 0.125 AC: 602 AN: 4814

European-Finnish (FIN) AF: 0.167 AC: 1764 AN: 10550

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14950 AN: 67966

Other (OTH) AF: 0.165 AC: 347 AN: 2108

Alfa AF: 0.0630 Hom.: 58

Bravo AF: 0.167

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		-0.086
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6594714; hg19: chr5-112738620;