NM_001414686.1:c.83-11460T>C

Variant names:

• chr19-9047528-A-G
• rs7249334
• NM_001414686.1:c.83-11460T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-9047528-A-G
• chrNW_025791807.1-297296-A-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.83-11460T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,066 control chromosomes in the GnomAD database, including 39,981 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 0.72 (39981 hom., cov: 32)
• Consequence: MUC16 NM_001414686.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 2 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414686.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC16	NM_001414686.1		c.83-11460T>C		intron	N/A	NP_001401615.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109108 AN: 151948 Hom.: 39941 Cov.: 32

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.718 AC: 109203 AN: 152066 Hom.: 39981 Cov.: 32 AF XY: 0.716 AC XY: 53225 AN XY: 74328

African (AFR) AF: 0.883 AC: 36652 AN: 41516

American (AMR) AF: 0.707 AC: 10783 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3049 AN: 5158

South Asian (SAS) AF: 0.593 AC: 2857 AN: 4818

European-Finnish (FIN) AF: 0.691 AC: 7308 AN: 10570

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44173 AN: 67974

Other (OTH) AF: 0.687 AC: 1452 AN: 2114

Alfa AF: 0.676 Hom.: 81195

Bravo AF: 0.728

Asia WGS AF: 0.588 AC: 2045 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	1.4
DANN	Benign	0.21
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs7249334; hg19: chr19-9158204;