rs182988

Variant names:

• chr5-113477869-T-A
• rs182988
• NM_001085377.2:c.170+10376A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-113477869-T-A
• chr5-113477869-T-C
• chr5-113477869-T-G

Variant summary

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

The NM_001085377.2(MCC):​c.170+10376A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,202 control chromosomes in the GnomAD database, including 57,891 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 0.87 (57891 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.170+10376A>T		intron_variant	Intron 1 of 18	ENST00000408903.7	NP_001078846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.170+10376A>T		intron_variant	Intron 1 of 18	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000511242.1	n.579+10376A>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132396 AN: 152084 Hom.: 57856 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.870 AC: 132484 AN: 152202 Hom.: 57891 Cov.: 32 AF XY: 0.869 AC XY: 64660 AN XY: 74402

African (AFR) AF: 0.838 AC: 34806 AN: 41540

American (AMR) AF: 0.927 AC: 14180 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3107 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5043 AN: 5184

South Asian (SAS) AF: 0.925 AC: 4463 AN: 4826

European-Finnish (FIN) AF: 0.777 AC: 8203 AN: 10556

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59673 AN: 68016

Other (OTH) AF: 0.884 AC: 1866 AN: 2112

Alfa AF: 0.860 Hom.: 6594

Bravo AF: 0.880

Asia WGS AF: 0.891 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.55
PhyloP100		0.45
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: rs182988; hg19: chr5-112813566;