5-113459655-A-T

Position:

• chr5-113459655-A-T

Variant summary

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

The NM_001085377.2(MCC):​c.170+28590T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,140 control chromosomes in the GnomAD database, including 2,105 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 (2105 hom., cov: 30)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCC	NM_001085377.2	c.170+28590T>A		intron_variant		ENST00000408903.7	NP_001078846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.170+28590T>A		intron_variant		2	NM_001085377.2	ENSP00000386227	P1
MCC	ENST00000511242.1	n.580-11368T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24331 AN: 152022 Hom.: 2103 Cov.: 30

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.160 AC: 24342 AN: 152140 Hom.: 2105 Cov.: 30 AF XY: 0.156 AC XY: 11615 AN XY: 74400

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0895

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0940 Hom.: 97

Bravo AF: 0.155

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.85

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: rs13174075; hg19: chr5-112795352; COSMIC: COSV68730062;