11-1199236-G-T

Variant names:

• chr11-1199236-G-T
• rs35288961
• NM_001304359.2:c.16395+51G>T

Variant summary

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

The NM_001304359.2(MUC5AC):​c.16395+51G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 724,058 control chromosomes in the GnomAD database, including 10,479 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 0.16 (2249 hom., cov: 32)
  • Exomes 𝑓: 0.15 (8230 hom.)
• Consequence: MUC5AC NM_001304359.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 6 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=-0.81).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	NM_001304359.2	MANE Select	c.16395+51G>T		intron	N/A	NP_001291288.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	ENST00000621226.2	TSL:5 MANE Select	c.16395+51G>T		intron	N/A	ENSP00000485659.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24575 AN: 151986 Hom.: 2249 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.155 AC: 88601 AN: 571954 Hom.: 8230 Cov.: 0 AF XY: 0.150 AC XY: 46572 AN XY: 310678

African (AFR) AF: 0.127 AC: 2116 AN: 16690

American (AMR) AF: 0.0898 AC: 3382 AN: 37666

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 1484 AN: 20224

East Asian (EAS) AF: 0.00372 AC: 126 AN: 33854

South Asian (SAS) AF: 0.0641 AC: 4155 AN: 64846

European-Finnish (FIN) AF: 0.246 AC: 8591 AN: 34896

Middle Eastern (MID) AF: 0.0912 AC: 323 AN: 3540

European-Non Finnish (NFE) AF: 0.193 AC: 63616 AN: 328904

Other (OTH) AF: 0.153 AC: 4808 AN: 31334

GnomAD4 genome AF: 0.162 AC: 24571 AN: 152104 Hom.: 2249 Cov.: 32 AF XY: 0.161 AC XY: 11988 AN XY: 74352

African (AFR) AF: 0.128 AC: 5298 AN: 41510

American (AMR) AF: 0.130 AC: 1992 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3472

East Asian (EAS) AF: 0.00425 AC: 22 AN: 5176

South Asian (SAS) AF: 0.0601 AC: 290 AN: 4826

European-Finnish (FIN) AF: 0.270 AC: 2849 AN: 10562

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13330 AN: 67954

Other (OTH) AF: 0.139 AC: 292 AN: 2106

Alfa AF: 0.178 Hom.: 295

Bravo AF: 0.151

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.85
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs35288961; hg19: chr11-1220462;