dbSNP rs80322456: MUC16:c.43647+9G>C (chr19-8851267-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_001401501.2(MUC16):c.43647+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,602,198 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.018 ( 88 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 73 hom. )

Consequence

MUC16
NM_001401501.2 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.212

Publications

0 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 (BayesDel_noAF=-0.71).

BP6

Variant 19-8851267-C-G is Benign according to our data. Variant chr19-8851267-C-G is described in ClinVar as Benign. ClinVar VariationId is 3044590.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.063 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	Effect	Exon Rank	Protein	UniProt
MUC16	NM_001401501.2	MANE Select	c.43647+9G>C	intron	N/A	NP_001388430.1	A0AAG2UXK0
MUC16	NM_001414686.1		c.44073+9G>C	intron	N/A	NP_001401615.1
MUC16	NM_001414687.1		c.43527+9G>C	intron	N/A	NP_001401616.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUC16	ENST00000397910.8	TSL:5	c.43425+9G>C	intron	N/A	ENSP00000381008.2	Q8WXI7
MUC16	ENST00000711672.1		c.43611+9G>C	intron	N/A	ENSP00000518832.1	A0AAA9YHI4
MUC16	ENST00000710609.1		c.43545+9G>C	intron	N/A	ENSP00000518375.1	A0AA34QW05

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2798

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0648

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00450

AC:

1067

AN:

237294

AF XY:

0.00343

show subpopulations

Gnomad AFR exome

AF:

0.0625

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00176

GnomAD4 exome

AF:

0.00182

AC:

2641

AN:

1449946

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1152

AN XY:

721124

show subpopulations

African (AFR)

AF:

0.0675

AC:

2222

AN:

32898

American (AMR)

AF:

0.00294

AC:

123

AN:

41870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25224

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.0000476

AC:

AN:

84042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53064

Middle Eastern (MID)

AF:

0.00158

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000596

AC:

AN:

1107760

Other (OTH)

AF:

0.00363

AC:

217

AN:

59780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

118

237

355

474

592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0185

AC:

2811

AN:

152252

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1325

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0650

AC:

2700

AN:

41542

American (AMR)

AF:

0.00471

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68010

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

128

255

383

510

638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00527

Hom.:

Bravo

AF:

0.0205

Asia WGS

AF:

0.00346

AC:

AN:

3478

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

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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