rs10854117

Positions:

• chr19-8902679-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001414686.1(MUC16):​c.39158-457C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,750 control chromosomes in the GnomAD database, including 5,622 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 0.27 (5622 hom., cov: 31)
• Consequence: MUC16 NM_001414686.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

Genes affected

MUC16 (HGNC:15582): (mucin 16, cell surface associated) This gene encodes a protein that is a member of the mucin family. Mucins are high molecular weight, O-glycosylated proteins that play an important role in forming a protective mucous barrier, and are found on the apical surfaces of the epithelia. The encoded protein is a membrane-tethered mucin that contains an extracellular domain at its amino terminus, a large tandem repeat domain, and a transmembrane domain with a short cytoplasmic domain. The amino terminus is highly glycosylated, while the repeat region contains 156 amino acid repeats unit that are rich in serines, threonines, and prolines. Interspersed within the repeats are Sea urchin sperm protein Enterokinase and Agrin (SEA) modules, leucine-rich repeats and ankyrin (ANK) repeats. These regions together form the ectodomain, and there is a potential cleavage site found near an SEA module close to the transmembrane domain. This protein is thought to play a role in forming a barrier, protecting epithelial cells from pathogens. Products of this gene have been used as a marker for different cancers, with higher expression levels associated with poorer outcomes. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC16	NM_001401501.2	c.38732-457C>T		intron_variant		ENST00000711671.1	NP_001388430.1
MUC16	NM_001414686.1	c.39158-457C>T		intron_variant			NP_001401615.1
MUC16	NM_001414687.1	c.38612-457C>T		intron_variant			NP_001401616.1
MUC16	NM_024690.2	c.38546-457C>T		intron_variant			NP_078966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC16	ENST00000711672.1	c.38732-457C>T		intron_variant				ENSP00000518832	A2
MUC16	ENST00000397910.8	c.38546-457C>T		intron_variant		5		ENSP00000381008	P2
MUC16	ENST00000710609.1	c.38666-457C>T		intron_variant				ENSP00000518375	A2
MUC16	ENST00000710610.1	c.29372-457C>T		intron_variant				ENSP00000518376	A2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40724 AN: 151632 Hom.: 5620 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.269 AC: 40747 AN: 151750 Hom.: 5622 Cov.: 31 AF XY: 0.269 AC XY: 19967 AN XY: 74158

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.279

Alfa AF: 0.295 Hom.: 9919

Bravo AF: 0.260

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.22

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: rs10854117; hg19: chr19-9013355; COSMIC: COSV67467261;