5-113402923-C-G

Position:

• chr5-113402923-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MCC	NM_001085377.2	c.171-17711G>C		intron_variant		ENST00000408903.7
LOC107986366	XR_001742459.2	n.59+2924C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCC	ENST00000408903.7	c.171-17711G>C		intron_variant		2	NM_001085377.2	P1
	ENST00000416046.2	n.303+2924C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.142

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: 0.0630 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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6594714; hg19: chr5-112738620;