rs10854117

Variant names:

• chr19-8902679-G-A
• rs10854117
• NM_001401501.2:c.38732-457C>T

Variant summary

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

The NM_001401501.2(MUC16):​c.38732-457C>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_001401501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001401501.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC16	NM_001401501.2	MANE Select	c.38732-457C>T		intron	N/A	NP_001388430.1
	MUC16	NM_001414686.1		c.39158-457C>T		intron	N/A	NP_001401615.1
	MUC16	NM_001414687.1		c.38612-457C>T		intron	N/A	NP_001401616.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC16	ENST00000397910.8	TSL:5	c.38546-457C>T		intron	N/A	ENSP00000381008.2
	MUC16	ENST00000711672.1		c.38732-457C>T		intron	N/A	ENSP00000518832.1
	MUC16	ENST00000710609.1		c.38666-457C>T		intron	N/A	ENSP00000518375.1

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

African (AFR) AF: 0.212 AC: 8750 AN: 41346

American (AMR) AF: 0.224 AC: 3406 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1175 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1356 AN: 5148

South Asian (SAS) AF: 0.291 AC: 1393 AN: 4786

European-Finnish (FIN) AF: 0.288 AC: 3035 AN: 10522

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20721 AN: 67938

Other (OTH) AF: 0.279 AC: 590 AN: 2112

Alfa AF: 0.287 Hom.: 15688

Bravo AF: 0.260

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.22
PhyloP100		0.26
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: rs10854117; hg19: chr19-9013355; COSMIC: COSV67467261;