rs1318772

Variant names:

• chr5-113387870-A-G
• rs1318772
• NM_001085377.2:c.171-2658T>C

Variant summary

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

The NM_001085377.2(MCC):​c.171-2658T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,166 control chromosomes in the GnomAD database, including 2,965 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 (2965 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

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=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.171-2658T>C		intron_variant	Intron 1 of 18	ENST00000408903.7	NP_001078846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.171-2658T>C		intron_variant	Intron 1 of 18	2	NM_001085377.2	ENSP00000386227.3
ENSG00000232633	ENST00000416046.2	n.247-12073A>G		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26220 AN: 152048 Hom.: 2953 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0787

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.173 AC: 26276 AN: 152166 Hom.: 2965 Cov.: 32 AF XY: 0.173 AC XY: 12886 AN XY: 74386

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0270

Gnomad4 SAS AF: 0.0782

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.148

Alfa AF: 0.122 Hom.: 2549

Bravo AF: 0.166

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.69

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: rs1318772; hg19: chr5-112723567; COSMIC: COSV68726526;