5-113211602-A-G

Variant names:

• chr5-113211602-A-G
• rs10519340
• NM_001085377.2:c.628-60180T>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.628-60180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 152,306 control chromosomes in the GnomAD database, including 803 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 0.059 (803 hom., cov: 32)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.628-60180T>C		intron_variant	Intron 3 of 18	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.58-60180T>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.628-60180T>C		intron_variant	Intron 3 of 18	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.58-60180T>C		intron_variant	Intron 1 of 16	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.-133+22835T>C		intron_variant	Intron 1 of 16	5		ENSP00000421615.2
MCC	ENST00000514701.5	c.58-60180T>C		intron_variant	Intron 1 of 13	2		ENSP00000485220.1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9018 AN: 152188 Hom.: 800 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.00951

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00676

Gnomad OTH AF: 0.0604

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

GnomAD4 genome AF: 0.0593 AC: 9037 AN: 152306 Hom.: 803 Cov.: 32 AF XY: 0.0577 AC XY: 4295 AN XY: 74476

African (AFR) AF: 0.189 AC: 7836 AN: 41532

American (AMR) AF: 0.0297 AC: 455 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5188

South Asian (SAS) AF: 0.00952 AC: 46 AN: 4834

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00676 AC: 460 AN: 68038

Other (OTH) AF: 0.0598 AC: 126 AN: 2108

Alfa AF: 0.0276 Hom.: 58

Bravo AF: 0.0683

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10519340; hg19: chr5-112547299;