NM_001085377.2:c.171-14322A>G

Variant names:

• chr5-113399534-T-C
• rs7714760
• NM_001085377.2:c.171-14322A>G

Variant summary

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

The NM_001085377.2(MCC):​c.171-14322A>G 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 152,106 control chromosomes in the GnomAD database, including 2,476 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 (2476 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 2 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=-1.05).
• 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.171-14322A>G		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.171-14322A>G		intron_variant	Intron 1 of 18	2	NM_001085377.2	ENSP00000386227.3
ENSG00000232633	ENST00000416046.3	n.247-409T>C		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26232 AN: 151988 Hom.: 2474 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0892

Gnomad SAS AF: 0.124

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: 0.173 AC: 26241 AN: 152106 Hom.: 2476 Cov.: 32 AF XY: 0.168 AC XY: 12491 AN XY: 74338

African (AFR) AF: 0.123 AC: 5102 AN: 41532

American (AMR) AF: 0.142 AC: 2170 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3470

East Asian (EAS) AF: 0.0892 AC: 462 AN: 5180

South Asian (SAS) AF: 0.125 AC: 602 AN: 4820

European-Finnish (FIN) AF: 0.167 AC: 1761 AN: 10554

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

European-Non Finnish (NFE) AF: 0.220 AC: 14949 AN: 67966

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.197 Hom.: 4784

Bravo AF: 0.168

Asia WGS AF: 0.0970 AC: 339 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.43
DANN	Benign	0.20
PhyloP100		-1.6
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: rs7714760; hg19: chr5-112735231;