chr11-1090879-A-G

Variant names:

• chr11-1090879-A-G
• rs7103978
• ENST00000675028.1:c.3600A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000675028.1(MUC2):​c.3600A>G​(p.Ala1200Ala) 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 ENST00000675028.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 14 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 -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 rank	MANE	Protein	UniProt
MUC2	NM_002457.5	c.3600A>G	p.Ala1200Ala	synonymous_variant	Exon 26 of 58		NP_002448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000675028.1	c.3600A>G	p.Ala1200Ala	synonymous_variant	Exon 26 of 30			ENSP00000502432.1
MUC2	ENST00000361558.7	n.3627A>G		non_coding_transcript_exon_variant	Exon 26 of 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

GnomAD2 exomes AF: 0.0754 AC: 18488 AN: 245298 AF XY: 0.0753

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 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

African (AFR) AF: 0.0630 AC: 2108 AN: 33452

American (AMR) AF: 0.0437 AC: 1946 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.0425 AC: 1107 AN: 26056

East Asian (EAS) AF: 0.0489 AC: 1940 AN: 39676

South Asian (SAS) AF: 0.0543 AC: 4663 AN: 85822

European-Finnish (FIN) AF: 0.116 AC: 6103 AN: 52706

Middle Eastern (MID) AF: 0.0411 AC: 237 AN: 5766

European-Non Finnish (NFE) AF: 0.0958 AC: 106459 AN: 1110986

Other (OTH) AF: 0.0826 AC: 4985 AN: 60322

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

African (AFR) AF: 0.0596 AC: 2475 AN: 41516

American (AMR) AF: 0.0601 AC: 919 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3470

East Asian (EAS) AF: 0.0611 AC: 316 AN: 5176

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4826

European-Finnish (FIN) AF: 0.113 AC: 1200 AN: 10622

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0953 AC: 6479 AN: 67996

Other (OTH) AF: 0.0754 AC: 159 AN: 2108

Alfa AF: 0.0837 Hom.: 1288

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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