Genetic Variant MCC:c.170+39935C>A (chr5-113448310-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001085377.2(MCC):c.170+39935C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,158 control chromosomes in the GnomAD database, including 2,102 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 ( 2101 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

MCC
NM_001085377.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

0 publications found

Variant links:

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]

MCC links:

LOC107986366 (HGNC:):

LOC107986366 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2 link	c.170+39935C>A		intron_variant	Intron 1 of 18	ENST00000408903.7	NP_001078846.2
LOC107986366	XR_001742459.2 link	n.261-453G>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7 link	c.170+39935C>A		intron_variant	Intron 1 of 18	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000511242.1 link	n.580-23C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24239

AN:

152038

Hom.:

2099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0893

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.159

AC:

24249

AN:

152156

Hom.:

2101

Cov.:

AF XY:

0.155

AC XY:

11564

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.116

AC:

4803

AN:

41542

American (AMR)

AF:

0.123

AC:

1882

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

477

AN:

3470

East Asian (EAS)

AF:

0.0893

AC:

462

AN:

5172

South Asian (SAS)

AF:

0.125

AC:

601

AN:

4814

European-Finnish (FIN)

AF:

0.159

AC:

1685

AN:

10584

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13728

AN:

67972

Other (OTH)

AF:

0.149

AC:

316

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1035

2071

3106

4142

5177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0630

Hom.:

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

-0.82

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over