rs1862456

Positions:

• chr19-8857873-A-C
• chr19-8857873-A-T

Variant summary

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

The NM_001414686.1(MUC16):​c.43784+331T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,666 control chromosomes in the GnomAD database, including 21,639 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 0.53 (21639 hom., cov: 30)
• Consequence: MUC16 NM_001414686.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC16	NM_001401501.2	c.43358+331T>G		intron_variant		ENST00000711671.1
MUC16	NM_001414686.1	c.43784+331T>G		intron_variant
MUC16	NM_001414687.1	c.43238+331T>G		intron_variant
MUC16	NM_024690.2	c.43136+331T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC16	ENST00000711672.1	c.43322+331T>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80727 AN: 151546 Hom.: 21637 Cov.: 30

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.532 AC: 80755 AN: 151666 Hom.: 21639 Cov.: 30 AF XY: 0.533 AC XY: 39472 AN XY: 74054

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.567

Alfa AF: 0.540 Hom.: 12824

Bravo AF: 0.526

Asia WGS AF: 0.629 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1862456; hg19: chr19-8968549;