chr19-8851305-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001401501.2(MUC16):c.43618G>C(p.Val14540Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 1,613,002 control chromosomes in the GnomAD database, including 689,345 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.92 ( 63904 hom., cov: 29)

Exomes 𝑓: 0.93 ( 625441 hom. )

Consequence

MUC16
NM_001401501.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.233

Publications

28 publications found

Variant links:

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]

MUC16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.8387624E-7).

BP6

Variant 19-8851305-C-G is Benign according to our data. Variant chr19-8851305-C-G is described in ClinVar as Benign. ClinVar VariationId is 3058931.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001401501.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC16	NM_001401501.2	MANE Select	c.43618G>C	p.Val14540Leu	missense	Exon 92 of 93	NP_001388430.1	A0AAG2UXK0
MUC16	NM_001414686.1		c.44044G>C	p.Val14682Leu	missense	Exon 93 of 94	NP_001401615.1
MUC16	NM_001414687.1		c.43498G>C	p.Val14500Leu	missense	Exon 89 of 90	NP_001401616.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC16	ENST00000397910.8	TSL:5	c.43396G>C	p.Val14466Leu	missense	Exon 83 of 84	ENSP00000381008.2	Q8WXI7
MUC16	ENST00000711672.1		c.43582G>C	p.Val14528Leu	missense	Exon 87 of 88	ENSP00000518832.1	A0AAA9YHI4
MUC16	ENST00000710609.1		c.43516G>C	p.Val14506Leu	missense	Exon 86 of 87	ENSP00000518375.1	A0AA34QW05

Frequencies

GnomAD3 genomes

AF:

0.917

AC:

139342

AN:

152012

Hom.:

63867

Cov.:

show subpopulations

Gnomad AFR

AF:

0.909

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.888

Gnomad ASJ

AF:

0.960

Gnomad EAS

AF:

0.902

Gnomad SAS

AF:

0.945

Gnomad FIN

AF:

0.910

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.927

Gnomad OTH

AF:

0.914

GnomAD2 exomes

AF:

0.919

AC:

228028

AN:

248236

AF XY:

0.923

show subpopulations

Gnomad AFR exome

AF:

0.904

Gnomad AMR exome

AF:

0.854

Gnomad ASJ exome

AF:

0.958

Gnomad EAS exome

AF:

0.906

Gnomad FIN exome

AF:

0.922

Gnomad NFE exome

AF:

0.931

Gnomad OTH exome

AF:

0.927

GnomAD4 exome

AF:

0.925

AC:

1351545

AN:

1460872

Hom.:

625441

Cov.:

AF XY:

0.927

AC XY:

673443

AN XY:

726764

show subpopulations

African (AFR)

AF:

0.904

AC:

30236

AN:

33452

American (AMR)

AF:

0.853

AC:

38064

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.958

AC:

24976

AN:

26074

East Asian (EAS)

AF:

0.913

AC:

36236

AN:

39684

South Asian (SAS)

AF:

0.945

AC:

81448

AN:

86188

European-Finnish (FIN)

AF:

0.921

AC:

49146

AN:

53338

Middle Eastern (MID)

AF:

0.953

AC:

5489

AN:

5760

European-Non Finnish (NFE)

AF:

0.927

AC:

1030053

AN:

1111428

Other (OTH)

AF:

0.926

AC:

55897

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

5581

11162

16744

22325

27906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21546

43092

64638

86184

107730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.917

AC:

139437

AN:

152130

Hom.:

63904

Cov.:

AF XY:

0.915

AC XY:

68068

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.909

AC:

37729

AN:

41502

American (AMR)

AF:

0.888

AC:

13567

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.960

AC:

3332

AN:

3470

East Asian (EAS)

AF:

0.902

AC:

4654

AN:

5158

South Asian (SAS)

AF:

0.945

AC:

4552

AN:

4816

European-Finnish (FIN)

AF:

0.910

AC:

9641

AN:

10592

Middle Eastern (MID)

AF:

0.939

AC:

276

AN:

294

European-Non Finnish (NFE)

AF:

0.927

AC:

63051

AN:

68004

Other (OTH)

AF:

0.913

AC:

1929

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

597

1194

1792

2389

2986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.926

Hom.:

49302

Bravo

AF:

0.912

TwinsUK

AF:

0.924

AC:

3427

ALSPAC

AF:

0.931

AC:

3587

ESP6500AA

AF:

0.915

AC:

3657

ESP6500EA

AF:

0.931

AC:

7765

ExAC

AF:

0.921

AC:

111321

Asia WGS

AF:

0.905

AC:

3149

AN:

3478

EpiCase

AF:

0.933

EpiControl

AF:

0.934

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MUC16-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.9

(source)

DANN

Benign

0.10

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.31

MetaRNN

Benign

6.8e-7

MetaSVM

Benign

-1.0

PhyloP100

0.23

PrimateAI

Benign

0.35

PROVEAN

Benign

1.8

REVEL

Benign

0.035

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.032

ClinPred

0.00030

GERP RS

-0.19

gMVP

0.19

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over