5-113181012-A-G

Variant names:

• chr5-113181012-A-G
• rs6594693
• NM_001085377.2:c.628-29590T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001085377.2(MCC):​c.628-29590T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,250 control chromosomes in the GnomAD database, including 65,931 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 0.93 (65931 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.628-29590T>C		intron_variant	Intron 3 of 18	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.58-29590T>C		intron_variant	Intron 1 of 16		NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.628-29590T>C		intron_variant	Intron 3 of 18	2	NM_001085377.2	ENSP00000386227.3

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141515 AN: 152132 Hom.: 65891 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.939

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

GnomAD4 genome AF: 0.930 AC: 141610 AN: 152250 Hom.: 65931 Cov.: 32 AF XY: 0.927 AC XY: 69020 AN XY: 74430

African (AFR) AF: 0.927 AC: 38498 AN: 41536

American (AMR) AF: 0.915 AC: 13987 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 3278 AN: 3472

East Asian (EAS) AF: 0.904 AC: 4688 AN: 5186

South Asian (SAS) AF: 0.928 AC: 4472 AN: 4818

European-Finnish (FIN) AF: 0.899 AC: 9531 AN: 10604

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64011 AN: 68024

Other (OTH) AF: 0.939 AC: 1984 AN: 2114

Alfa AF: 0.941 Hom.: 111723

Bravo AF: 0.932

Asia WGS AF: 0.893 AC: 3104 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		1.6
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: rs6594693; hg19: chr5-112516709;