5-113245183-C-T

Variant names:

• chr5-113245183-C-T
• rs11743052
• NM_001085377.2:c.628-93761G>A

Variant summary

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

The NM_001085377.2(MCC):​c.628-93761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,578 control chromosomes in the GnomAD database, including 2,268 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 0.16 (2268 hom., cov: 31)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.628-93761G>A		intron_variant	Intron 3 of 18	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.57+49146G>A		intron_variant	Intron 1 of 16		NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.628-93761G>A		intron_variant	Intron 3 of 18	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.57+49146G>A		intron_variant	Intron 1 of 16	1		ENSP00000305617.4
MCC	ENST00000514701.5	c.57+49146G>A		intron_variant	Intron 1 of 13	2		ENSP00000485220.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24134 AN: 151460 Hom.: 2261 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.0701

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.159 AC: 24156 AN: 151578 Hom.: 2268 Cov.: 31 AF XY: 0.162 AC XY: 11962 AN XY: 74032

African (AFR) AF: 0.190 AC: 7825 AN: 41268

American (AMR) AF: 0.293 AC: 4463 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 242 AN: 3466

East Asian (EAS) AF: 0.0700 AC: 361 AN: 5154

South Asian (SAS) AF: 0.113 AC: 540 AN: 4794

European-Finnish (FIN) AF: 0.146 AC: 1529 AN: 10458

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8780 AN: 67892

Other (OTH) AF: 0.145 AC: 305 AN: 2098

Alfa AF: 0.0727 Hom.: 85

Bravo AF: 0.172

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.43
PhyloP100		-1.4
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: rs11743052; hg19: chr5-112580880;