dbSNP rs1132440: MUC5AC:p.Arg5618Arg (chr11-1200591-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001304359.2(MUC5AC):c.16854G>C(p.Arg5618Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 764,098 control chromosomes in the GnomAD database, including 126,999 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 0.52 ( 21612 hom., cov: 34)

Exomes 𝑓: 0.58 ( 105387 hom. )

Consequence

MUC5AC
NM_001304359.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.666

Publications

16 publications found

Variant links:

Genes affected

MUC5AC (HGNC:7515): (mucin 5AC, oligomeric mucus/gel-forming) Predicted to be an extracellular matrix structural constituent. Involved in phosphatidylinositol-mediated signaling. Located in cytoplasm; extracellular space; and mucus layer. Implicated in dry eye syndrome. Biomarker of several diseases, including Sjogren's syndrome; biliary tract disease (multiple); cystic fibrosis; eye disease (multiple); and pancreatic cancer (multiple). [provided by Alliance of Genome Resources, Apr 2022]

MUC5AC 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=-0.86).

BP7

Synonymous conserved (PhyloP=-0.666 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5AC	NM_001304359.2 link	c.16854G>C	p.Arg5618Arg	synonymous_variant	Exon 49 of 49	ENST00000621226.2	NP_001291288.1	P98088

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5AC	ENST00000621226.2 link	c.16854G>C	p.Arg5618Arg	synonymous_variant	Exon 49 of 49	5	NM_001304359.2	ENSP00000485659.1		P98088

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79168

AN:

151950

Hom.:

21624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.597

Gnomad OTH

AF:

0.543

GnomAD2 exomes

AF:

0.578

AC:

130669

AN:

226102

AF XY:

0.581

show subpopulations

Gnomad AFR exome

AF:

0.333

Gnomad AMR exome

AF:

0.576

Gnomad ASJ exome

AF:

0.685

Gnomad EAS exome

AF:

0.692

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.601

Gnomad OTH exome

AF:

0.588

GnomAD4 exome

AF:

0.582

AC:

356436

AN:

612030

Hom.:

105387

Cov.:

AF XY:

0.582

AC XY:

194631

AN XY:

334536

show subpopulations

African (AFR)

AF:

0.328

AC:

5794

AN:

17682

American (AMR)

AF:

0.576

AC:

25120

AN:

43634

Ashkenazi Jewish (ASJ)

AF:

0.684

AC:

14330

AN:

20936

East Asian (EAS)

AF:

0.654

AC:

23592

AN:

36054

South Asian (SAS)

AF:

0.527

AC:

36741

AN:

69730

European-Finnish (FIN)

AF:

0.555

AC:

20799

AN:

37484

Middle Eastern (MID)

AF:

0.582

AC:

2407

AN:

4138

European-Non Finnish (NFE)

AF:

0.597

AC:

208783

AN:

349464

Other (OTH)

AF:

0.573

AC:

18870

AN:

32908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

9004

18007

27011

36014

45018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1186

2372

3558

4744

5930

<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:

0.521

AC:

79173

AN:

152068

Hom.:

21612

Cov.:

AF XY:

0.517

AC XY:

38448

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.336

AC:

13944

AN:

41498

American (AMR)

AF:

0.575

AC:

8790

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.692

AC:

2402

AN:

3470

East Asian (EAS)

AF:

0.670

AC:

3453

AN:

5154

South Asian (SAS)

AF:

0.499

AC:

2408

AN:

4826

European-Finnish (FIN)

AF:

0.543

AC:

5753

AN:

10592

Middle Eastern (MID)

AF:

0.620

AC:

181

AN:

292

European-Non Finnish (NFE)

AF:

0.597

AC:

40576

AN:

67920

Other (OTH)

AF:

0.540

AC:

1142

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1868

3735

5603

7470

9338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.570

Hom.:

4651

Bravo

AF:

0.520

Asia WGS

AF:

0.482

AC:

1678

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.38

(source)

DANN

Benign

0.66

PhyloP100

-0.67

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over