NM_001414686.1:c.43784+331T>G

Variant names:

• chr19-8857873-A-C
• rs1862456
• NM_001401501.2:c.43358+331T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-8857873-A-C
• chrNW_025791807.1-122687-A-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 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_001401501.2	MANE Select	c.43358+331T>G		intron	N/A	NP_001388430.1	A0AAG2UXK0
	MUC16	NM_001414686.1		c.43784+331T>G		intron	N/A	NP_001401615.1
	MUC16	NM_001414687.1		c.43238+331T>G		intron	N/A	NP_001401616.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC16	ENST00000397910.8	TSL:5	c.43136+331T>G		intron	N/A	ENSP00000381008.2	Q8WXI7
	MUC16	ENST00000711672.1		c.43322+331T>G		intron	N/A	ENSP00000518832.1	A0AAA9YHI4
	MUC16	ENST00000710609.1		c.43256+331T>G		intron	N/A	ENSP00000518375.1	A0AA34QW05

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

African (AFR) AF: 0.470 AC: 19441 AN: 41374

American (AMR) AF: 0.502 AC: 7642 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3470

East Asian (EAS) AF: 0.600 AC: 3078 AN: 5130

South Asian (SAS) AF: 0.650 AC: 3119 AN: 4800

European-Finnish (FIN) AF: 0.541 AC: 5656 AN: 10454

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.558 AC: 37896 AN: 67922

Other (OTH) AF: 0.567 AC: 1187 AN: 2092

Alfa AF: 0.546 Hom.: 18786

Bravo AF: 0.526

Asia WGS AF: 0.629 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.58
PhyloP100		-0.018
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1862456; hg19: chr19-8968549;