rs7103978

chr11-1090879-A-Gchr11-1090879-A-T

Variant summary

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

The NM_002457.5(MUC2):c.3600A>G(p.Ala1200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 1,611,516 control chromosomes in the GnomAD database, including 6,612 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 0.079 (512 hom., cov: 34)
  • Exomes 𝑓: 0.089 (6100 hom.)
• Consequence: MUC2 NM_002457.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC2	NM_002457.5	c.3600A>G	p.Ala1200=	synonymous_variant	26/58	ENST00000713550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC2	ENST00000675028.1	c.3600A>G	p.Ala1200=	synonymous_variant	26/30			P3
MUC2	ENST00000361558.7	n.3627A>G		non_coding_transcript_exon_variant	26/49	5

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11962 AN: 152100 Hom.: 509 Cov.: 34

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.0542

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0953

Gnomad OTH AF: 0.0738

GnomAD3 exomes AF: 0.0754 AC: 18488 AN: 245298 Hom.: 784 AF XY: 0.0753 AC XY: 10056 AN XY: 133536

Gnomad AFR exome AF: 0.0617

Gnomad AMR exome AF: 0.0414

Gnomad ASJ exome AF: 0.0432

Gnomad EAS exome AF: 0.0660

Gnomad SAS exome AF: 0.0541

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.0900

Gnomad OTH exome AF: 0.0815

GnomAD4 exome AF: 0.0888 AC: 129548 AN: 1459298 Hom.: 6100 Cov.: 33 AF XY: 0.0877 AC XY: 63666 AN XY: 725746

Gnomad4 AFR exome AF: 0.0630

Gnomad4 AMR exome AF: 0.0437

Gnomad4 ASJ exome AF: 0.0425

Gnomad4 EAS exome AF: 0.0489

Gnomad4 SAS exome AF: 0.0543

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.0958

Gnomad4 OTH exome AF: 0.0826

GnomAD4 genome AF: 0.0787 AC: 11981 AN: 152218 Hom.: 512 Cov.: 34 AF XY: 0.0784 AC XY: 5837 AN XY: 74418

Gnomad4 AFR AF: 0.0596

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0953

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0831 Hom.: 972

Bravo AF: 0.0739

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.050
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7103978; hg19: chr11-1088815; COSMIC: COSV61250128;