chr5-113245556-G-C

Position:

• chr5-113245556-G-C

Variant summary

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

The NM_001085377.2(MCC):​c.628-94134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 151,918 control chromosomes in the GnomAD database, including 252 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 0.035 (252 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCC	NM_001085377.2	c.628-94134C>G		intron_variant		ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.57+48773C>G		intron_variant			NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.628-94134C>G		intron_variant		2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.57+48773C>G		intron_variant		1		ENSP00000305617.4
MCC	ENST00000514701.5	c.57+48773C>G		intron_variant		2		ENSP00000485220.1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5301 AN: 151800 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00586

Gnomad OTH AF: 0.0331

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

GnomAD4 genome AF: 0.0349 AC: 5306 AN: 151918 Hom.: 252 Cov.: 32 AF XY: 0.0340 AC XY: 2521 AN XY: 74254

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00484

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0000949

Gnomad4 NFE AF: 0.00586

Gnomad4 OTH AF: 0.0328

Alfa AF: 0.000444 Hom.: 0

Bravo AF: 0.0410

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.65

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: rs10519342; hg19: chr5-112581253;