chr11-1075747-C-T

Variant names:

• chr11-1075747-C-T
• rs2856111
• ENST00000675028.1:c.173C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000675028.1(MUC2):​c.173C>T​(p.Pro58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,609,964 control chromosomes in the GnomAD database, including 581,143 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (48650 hom., cov: 35)
  • Exomes 𝑓: 0.85 (532493 hom.)
• Consequence: MUC2 ENST00000675028.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903
• Publications: 30 publications found

Genes affected

MUC2 (HGNC:7512): (mucin 2, oligomeric mucus/gel-forming) This gene encodes a member of the mucin protein family. Mucins are high molecular weight glycoproteins produced by many epithelial tissues. The protein encoded by this gene is secreted and forms an insoluble mucous barrier that protects the gut lumen. The protein polymerizes into a gel of which 80% is composed of oligosaccharide side chains by weight. The protein features a central domain containing tandem repeats rich in threonine and proline that varies between 50 and 115 copies in different individuals. Downregulation of this gene has been observed in patients with Crohn disease and ulcerative colitis. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC2	NM_002457.5	c.173C>T	p.Pro58Leu	missense_variant	Exon 2 of 58		NP_002448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000675028.1	c.173C>T	p.Pro58Leu	missense_variant	Exon 2 of 30			ENSP00000502432.1
MUC2	ENST00000361558.7	n.200C>T		non_coding_transcript_exon_variant	Exon 2 of 49	5

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120367 AN: 152094 Hom.: 48625 Cov.: 35

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.828

GnomAD4 exome AF: 0.852 AC: 1242079 AN: 1457750 Hom.: 532493 Cov.: 75 AF XY: 0.852 AC XY: 617823 AN XY: 724918

African (AFR) AF: 0.625 AC: 20892 AN: 33418

American (AMR) AF: 0.891 AC: 39587 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 22699 AN: 26020

East Asian (EAS) AF: 0.530 AC: 20960 AN: 39526

South Asian (SAS) AF: 0.832 AC: 71246 AN: 85608

European-Finnish (FIN) AF: 0.826 AC: 42863 AN: 51862

Middle Eastern (MID) AF: 0.860 AC: 4953 AN: 5758

European-Non Finnish (NFE) AF: 0.872 AC: 968315 AN: 1110884

Other (OTH) AF: 0.839 AC: 50564 AN: 60240

GnomAD4 genome AF: 0.791 AC: 120452 AN: 152214 Hom.: 48650 Cov.: 35 AF XY: 0.790 AC XY: 58807 AN XY: 74424

African (AFR) AF: 0.637 AC: 26435 AN: 41510

American (AMR) AF: 0.864 AC: 13224 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3051 AN: 3468

East Asian (EAS) AF: 0.533 AC: 2741 AN: 5142

South Asian (SAS) AF: 0.839 AC: 4049 AN: 4828

European-Finnish (FIN) AF: 0.825 AC: 8762 AN: 10618

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59382 AN: 68016

Other (OTH) AF: 0.828 AC: 1753 AN: 2116

Alfa AF: 0.847 Hom.: 180884

Bravo AF: 0.786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	13
PhyloP100		0.90

Splicing

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

Other links and lift over

dbSNP: rs2856111; hg19: chr11-1075747;