5-113472920-A-T

Position:

• chr5-113472920-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+15325T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,226 control chromosomes in the GnomAD database, including 63,411 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 0.91 (63411 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCC	NM_001085377.2	c.170+15325T>A		intron_variant		ENST00000408903.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCC	ENST00000408903.7	c.170+15325T>A		intron_variant		2	NM_001085377.2	P1
MCC	ENST00000511242.1	n.579+15325T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138495 AN: 152108 Hom.: 63350 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.911 AC: 138615 AN: 152226 Hom.: 63411 Cov.: 32 AF XY: 0.908 AC XY: 67581 AN XY: 74412

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.917

Alfa AF: 0.885 Hom.: 7445

Bravo AF: 0.926

Asia WGS AF: 0.928 AC: 3225 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.77
DANN	Benign	0.59

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: rs414475; hg19: chr5-112808617;