11-1193124-A-G

Variant names:

• chr11-1193124-A-G
• rs35705491
• NM_001304359.2:c.14580+142A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304359.2(MUC5AC):​c.14580+142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 593,202 control chromosomes in the GnomAD database, including 9,135 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 0.17 (2432 hom., cov: 33)
  • Exomes 𝑓: 0.16 (6703 hom.)
• Consequence: MUC5AC NM_001304359.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	NM_001304359.2	MANE Select	c.14580+142A>G		intron	N/A	NP_001291288.1	P98088

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	ENST00000621226.2	TSL:5 MANE Select	c.14580+142A>G		intron	N/A	ENSP00000485659.1	P98088

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25902 AN: 152168 Hom.: 2426 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.160 AC: 70435 AN: 440916 Hom.: 6703 AF XY: 0.154 AC XY: 35535 AN XY: 231202

African (AFR) AF: 0.157 AC: 1935 AN: 12348

American (AMR) AF: 0.106 AC: 2017 AN: 18954

Ashkenazi Jewish (ASJ) AF: 0.0768 AC: 1048 AN: 13650

East Asian (EAS) AF: 0.00384 AC: 119 AN: 30994

South Asian (SAS) AF: 0.0627 AC: 2800 AN: 44670

European-Finnish (FIN) AF: 0.245 AC: 7172 AN: 29318

Middle Eastern (MID) AF: 0.0814 AC: 158 AN: 1940

European-Non Finnish (NFE) AF: 0.194 AC: 51157 AN: 263364

Other (OTH) AF: 0.157 AC: 4029 AN: 25678

GnomAD4 genome AF: 0.170 AC: 25927 AN: 152286 Hom.: 2432 Cov.: 33 AF XY: 0.170 AC XY: 12653 AN XY: 74462

African (AFR) AF: 0.157 AC: 6545 AN: 41562

American (AMR) AF: 0.134 AC: 2053 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3470

East Asian (EAS) AF: 0.00443 AC: 23 AN: 5188

South Asian (SAS) AF: 0.0600 AC: 290 AN: 4830

European-Finnish (FIN) AF: 0.271 AC: 2868 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13343 AN: 68008

Other (OTH) AF: 0.145 AC: 307 AN: 2114

Alfa AF: 0.174 Hom.: 2321

Bravo AF: 0.161

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.19
PhyloP100		-0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35705491; hg19: chr11-1214349;