5-113244593-T-C

Position:

• chr5-113244593-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001085377.2(MCC):​c.628-93171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 152,336 control chromosomes in the GnomAD database, including 58 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 0.025 (58 hom., cov: 33)
• Consequence: MCC NM_001085377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.6).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0246 (3754/152336) while in subpopulation NFE AF= 0.0361 (2455/68032). AF 95% confidence interval is 0.0349. There are 58 homozygotes in gnomad4. There are 1810 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCC	NM_001085377.2	c.628-93171A>G		intron_variant		ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.57+49736A>G		intron_variant			NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.628-93171A>G		intron_variant		2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.57+49736A>G		intron_variant		1		ENSP00000305617.4
MCC	ENST00000514701.5	c.57+49736A>G		intron_variant		2		ENSP00000485220.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3755 AN: 152218 Hom.: 58 Cov.: 33

Gnomad AFR AF: 0.00733

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0246 AC: 3754 AN: 152336 Hom.: 58 Cov.: 33 AF XY: 0.0243 AC XY: 1810 AN XY: 74480

Gnomad4 AFR AF: 0.00731

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0361

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0323 Hom.: 48

Bravo AF: 0.0205

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.88

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: rs17323670; hg19: chr5-112580290;