rs3209874

Positions:

• chr5-113023193-C-T

Variant summary

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

The NM_001085377.2(MCC):​c.*4109G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,182 control chromosomes in the GnomAD database, including 2,136 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 (2136 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MCC NM_001085377.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCC	NM_001085377.2	c.*4109G>A		3_prime_UTR_variant	19/19	ENST00000408903.7
MCC	NM_002387.3	c.*4109G>A		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCC	ENST00000408903.7	c.*4109G>A		3_prime_UTR_variant	19/19	2	NM_001085377.2	P1
MCC	ENST00000302475.9	c.*4109G>A		3_prime_UTR_variant	17/17	1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23911 AN: 152064 Hom.: 2134 Cov.: 33

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.148

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.157 AC: 23913 AN: 152182 Hom.: 2136 Cov.: 33 AF XY: 0.152 AC XY: 11302 AN XY: 74390

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.154

Alfa AF: 0.202 Hom.: 4256

Bravo AF: 0.154

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3209874; hg19: chr5-112358890; COSMIC: COSV56725771; COSMIC: COSV56725771;