11-1090036-T-C

Position:

• chr11-1090036-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002457.5(MUC2):​c.3447T>C​(p.Asn1149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 1,611,784 control chromosomes in the GnomAD database, including 487,635 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 0.73 (41439 hom., cov: 33)
  • Exomes 𝑓: 0.78 (446196 hom.)
• Consequence: MUC2 NM_002457.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-2.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC2	NM_002457.5	c.3447T>C	p.Asn1149=	synonymous_variant	25/58	ENST00000713550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC2	ENST00000675028.1	c.3447T>C	p.Asn1149=	synonymous_variant	25/30			P3
MUC2	ENST00000361558.7	n.3474T>C		non_coding_transcript_exon_variant	25/49	5

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111490 AN: 152008 Hom.: 41429 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.746

GnomAD4 exome AF: 0.780 AC: 1137865 AN: 1459658 Hom.: 446196 Cov.: 67 AF XY: 0.780 AC XY: 566100 AN XY: 725998

Gnomad4 AFR exome AF: 0.641

Gnomad4 AMR exome AF: 0.621

Gnomad4 ASJ exome AF: 0.845

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.731

Gnomad4 FIN exome AF: 0.764

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.773

GnomAD4 genome AF: 0.733 AC: 111544 AN: 152126 Hom.: 41439 Cov.: 33 AF XY: 0.729 AC XY: 54223 AN XY: 74384

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.746

Alfa AF: 0.783 Hom.: 61195

Bravo AF: 0.720

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.088

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10902088; hg19: chr11-1087972;