Genetic Variant MUC5AC:c.14580+142A>C (chr11-1193124-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304359.2(MUC5AC):c.14580+142A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000227 in 441,144 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

MUC5AC
NM_001304359.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.411

Publications

8 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5AC	NM_001304359.2 link	c.14580+142A>C		intron_variant	Intron 32 of 48	ENST00000621226.2	NP_001291288.1	P98088

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5AC	ENST00000621226.2 link	c.14580+142A>C		intron_variant	Intron 32 of 48	5	NM_001304359.2	ENSP00000485659.1		P98088

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000227

AC:

AN:

441144

Hom.:

AF XY:

0.00000432

AC XY:

AN XY:

231312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12352

American (AMR)

AF:

0.00

AC:

AN:

18958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13654

East Asian (EAS)

AF:

0.00

AC:

AN:

30994

South Asian (SAS)

AF:

0.00

AC:

AN:

44686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1942

European-Non Finnish (NFE)

AF:

0.00000379

AC:

AN:

263508

Other (OTH)

AF:

0.00

AC:

AN:

25700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

2321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.82

(source)

DANN

Benign

0.31

PhyloP100

-0.41

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over