Genetic Variant NM_001304359.2:c.1490C>T (chr11-1167980-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001304359.2(MUC5AC):c.1490C>T(p.Ala497Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,550,168 control chromosomes in the GnomAD database, including 1,506 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.033 ( 109 hom., cov: 34)

Exomes 𝑓: 0.041 ( 1397 hom. )

Consequence

MUC5AC
NM_001304359.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

Publications

12 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004837781).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304359.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	NM_001304359.2	MANE Select	c.1490C>T	p.Ala497Val	missense	Exon 12 of 49	NP_001291288.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	ENST00000621226.2	TSL:5 MANE Select	c.1490C>T	p.Ala497Val	missense	Exon 12 of 49	ENSP00000485659.1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5030

AN:

152148

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00697

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.0350

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.0418

Gnomad MID

AF:

0.0924

Gnomad NFE

AF:

0.0427

Gnomad OTH

AF:

0.0402

GnomAD4 exome

AF:

0.0414

AC:

57824

AN:

1397902

Hom.:

1397

Cov.:

AF XY:

0.0420

AC XY:

28974

AN XY:

689472

show subpopulations

African (AFR)

AF:

0.00554

AC:

175

AN:

31594

American (AMR)

AF:

0.0307

AC:

1096

AN:

35714

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

2576

AN:

25186

East Asian (EAS)

AF:

0.000168

AC:

AN:

35748

South Asian (SAS)

AF:

0.0559

AC:

4427

AN:

79228

European-Finnish (FIN)

AF:

0.0421

AC:

2009

AN:

47708

Middle Eastern (MID)

AF:

0.0781

AC:

445

AN:

5698

European-Non Finnish (NFE)

AF:

0.0411

AC:

44363

AN:

1079010

Other (OTH)

AF:

0.0470

AC:

2727

AN:

58016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

3142

6285

9427

12570

15712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1666

3332

4998

6664

8330

<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:

0.0330

AC:

5026

AN:

152266

Hom.:

109

Cov.:

AF XY:

0.0329

AC XY:

2446

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00695

AC:

289

AN:

41558

American (AMR)

AF:

0.0350

AC:

535

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

347

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0498

AC:

240

AN:

4820

European-Finnish (FIN)

AF:

0.0418

AC:

444

AN:

10614

Middle Eastern (MID)

AF:

0.0925

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0426

AC:

2900

AN:

68010

Other (OTH)

AF:

0.0384

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

252

503

755

1006

1258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0396

Hom.:

Bravo

AF:

0.0325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_noAF

Benign

-0.95

CADD

Benign

(source)

DEOGEN2

Benign

0.22

MetaRNN

Benign

0.0048

PhyloP100

2.5

Sift4G

Uncertain

0.027

Vest4

0.064

gMVP

0.55

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over