rs4078252

Variant names:

• chr5-113119770-C-T
• rs4078252
• NM_001085377.2:c.1027+2914G>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.1027+2914G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,110 control chromosomes in the GnomAD database, including 6,013 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 0.26 (6013 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085377.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCC	NM_001085377.2	MANE Select	c.1027+2914G>A		intron	N/A	NP_001078846.2	P23508-2
	MCC	NM_002387.3		c.457+2914G>A		intron	N/A	NP_002378.2	P23508-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCC	ENST00000408903.7	TSL:2 MANE Select	c.1027+2914G>A		intron	N/A	ENSP00000386227.3	P23508-2
	MCC	ENST00000302475.9	TSL:1	c.457+2914G>A		intron	N/A	ENSP00000305617.4	P23508-1
	MCC	ENST00000515367.6	TSL:5	c.268+2914G>A		intron	N/A	ENSP00000421615.2	D6REY2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39724 AN: 151996 Hom.: 6016 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.261 AC: 39720 AN: 152110 Hom.: 6013 Cov.: 32 AF XY: 0.266 AC XY: 19759 AN XY: 74338

African (AFR) AF: 0.123 AC: 5119 AN: 41534

American (AMR) AF: 0.241 AC: 3691 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1133 AN: 3472

East Asian (EAS) AF: 0.139 AC: 720 AN: 5172

South Asian (SAS) AF: 0.394 AC: 1897 AN: 4814

European-Finnish (FIN) AF: 0.397 AC: 4186 AN: 10544

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22072 AN: 67958

Other (OTH) AF: 0.272 AC: 574 AN: 2112

Alfa AF: 0.282 Hom.: 2182

Bravo AF: 0.240

Asia WGS AF: 0.261 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.80
PhyloP100		-0.53
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: rs4078252; hg19: chr5-112455467; COSMIC: COSV56726072;