Genetic Variant 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:

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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

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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