rs10854117

Variant names:

• chr19-8902679-G-A
• rs10854117
• NM_001414686.1:c.39158-457C>T

Variant summary

Our verdict is Benign. The variant received -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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC16	NM_001414686.1	c.39158-457C>T		intron_variant	Intron 38 of 93		NP_001401615.1
MUC16	NM_001401501.2	c.38732-457C>T		intron_variant	Intron 37 of 92		NP_001388430.1
MUC16	NM_001414687.1	c.38612-457C>T		intron_variant	Intron 34 of 89		NP_001401616.1
MUC16	NM_024690.2	c.38546-457C>T		intron_variant	Intron 33 of 83		NP_078966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC16	ENST00000710609.1	c.38666-457C>T		intron_variant	Intron 36 of 86			ENSP00000518375.1
MUC16	ENST00000397910.8	c.38546-457C>T		intron_variant	Intron 33 of 83	5		ENSP00000381008.2
MUC16	ENST00000710610.1	c.29372-457C>T		intron_variant	Intron 35 of 85			ENSP00000518376.1

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

Gnomad4 AFR AF: 0.212 AC: 0.211629 AN: 0.211629

Gnomad4 AMR AF: 0.224 AC: 0.223667 AN: 0.223667

Gnomad4 ASJ AF: 0.339 AC: 0.338812 AN: 0.338812

Gnomad4 EAS AF: 0.263 AC: 0.263403 AN: 0.263403

Gnomad4 SAS AF: 0.291 AC: 0.291057 AN: 0.291057

Gnomad4 FIN AF: 0.288 AC: 0.288443 AN: 0.288443

Gnomad4 NFE AF: 0.305 AC: 0.304999 AN: 0.304999

Gnomad4 OTH AF: 0.279 AC: 0.279356 AN: 0.279356

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 v4.3

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

Publications

LitVar

Other links and lift over

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