chr11-1084609-G-A

Variant names:

• chr11-1084609-G-A
• rs41480348
• ENST00000675028.1:c.1854G>A

Variant summary

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

The ENST00000675028.1(MUC2):​c.1854G>A​(p.Thr618Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 1,612,466 control chromosomes in the GnomAD database, including 5,466 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 0.059 (374 hom., cov: 35)
  • Exomes 𝑓: 0.079 (5092 hom.)
• Consequence: MUC2 ENST00000675028.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 7 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=-0.58).
• BP7: Synonymous conserved (PhyloP=-1.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC2	NM_002457.5	c.1854G>A	p.Thr618Thr	synonymous_variant	Exon 15 of 58		NP_002448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000675028.1	c.1854G>A	p.Thr618Thr	synonymous_variant	Exon 15 of 30			ENSP00000502432.1
MUC2	ENST00000361558.7	n.1881G>A		non_coding_transcript_exon_variant	Exon 15 of 49	5

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8989 AN: 152206 Hom.: 375 Cov.: 35

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.0603

GnomAD2 exomes AF: 0.0621 AC: 15369 AN: 247600 AF XY: 0.0628

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0449

Gnomad ASJ exome AF: 0.0835

Gnomad EAS exome AF: 0.000223

Gnomad FIN exome AF: 0.0726

Gnomad NFE exome AF: 0.0869

Gnomad OTH exome AF: 0.0731

GnomAD4 exome AF: 0.0791 AC: 115506 AN: 1460142 Hom.: 5092 Cov.: 39 AF XY: 0.0781 AC XY: 56752 AN XY: 726350

African (AFR) AF: 0.0132 AC: 441 AN: 33478

American (AMR) AF: 0.0466 AC: 2083 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0819 AC: 2140 AN: 26116

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39696

South Asian (SAS) AF: 0.0356 AC: 3067 AN: 86230

European-Finnish (FIN) AF: 0.0682 AC: 3552 AN: 52076

Middle Eastern (MID) AF: 0.0496 AC: 286 AN: 5768

European-Non Finnish (NFE) AF: 0.0896 AC: 99592 AN: 1111746

Other (OTH) AF: 0.0719 AC: 4341 AN: 60346

GnomAD4 genome AF: 0.0590 AC: 8980 AN: 152324 Hom.: 374 Cov.: 35 AF XY: 0.0572 AC XY: 4260 AN XY: 74482

African (AFR) AF: 0.0151 AC: 629 AN: 41582

American (AMR) AF: 0.0637 AC: 974 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 280 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0299 AC: 144 AN: 4824

European-Finnish (FIN) AF: 0.0754 AC: 801 AN: 10624

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0872 AC: 5932 AN: 68020

Other (OTH) AF: 0.0597 AC: 126 AN: 2112

Alfa AF: 0.0762 Hom.: 352

Bravo AF: 0.0572

Asia WGS AF: 0.0140 AC: 51 AN: 3478

EpiCase AF: 0.0839

EpiControl AF: 0.0871

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.11
DANN	Benign	0.86
PhyloP100		-1.6
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs41480348; hg19: chr11-1082605;