19-9045019-T-C

Variant names:

• chr19-9045019-T-C
• rs8102472
• NM_001414686.1:c.83-8951A>G

Variant summary

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

The NM_001414686.1(MUC16):​c.83-8951A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,148 control chromosomes in the GnomAD database, including 42,315 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 0.74 (42315 hom., cov: 32)
• Consequence: MUC16 NM_001414686.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.02
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC16	NM_001414686.1	c.83-8951A>G		intron_variant	Intron 1 of 93		NP_001401615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112239 AN: 152030 Hom.: 42275 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.738 AC: 112333 AN: 152148 Hom.: 42315 Cov.: 32 AF XY: 0.735 AC XY: 54648 AN XY: 74372

African (AFR) AF: 0.907 AC: 37681 AN: 41558

American (AMR) AF: 0.723 AC: 11041 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2128 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3024 AN: 5150

South Asian (SAS) AF: 0.602 AC: 2890 AN: 4804

European-Finnish (FIN) AF: 0.704 AC: 7468 AN: 10604

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45814 AN: 67984

Other (OTH) AF: 0.708 AC: 1493 AN: 2110

Alfa AF: 0.709 Hom.: 4851

Bravo AF: 0.749

Asia WGS AF: 0.577 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0080
DANN	Benign	0.60
PhyloP100		-5.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8102472; hg19: chr19-9155695;