11-1094482-G-T

Variant names:

• chr11-1094482-G-T
• rs75494928
• NM_002457.5:c.4239G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_002457.5(MUC2):​c.4239G>T​(p.Thr1413Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1413T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC2 NM_002457.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 0 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]

ENSG00000296903 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-2.73 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002457.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	NM_002457.5	MANE Select	c.4239G>T	p.Thr1413Thr	synonymous	Exon 30 of 58	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000361558.7	TSL:5	n.4266G>T		non_coding_transcript_exon	Exon 30 of 49
	ENSG00000296903	ENST00000743440.1		n.141-161C>A		intron	N/A
	MUC2	ENST00000675028.1		c.*57G>T		downstream_gene	N/A	ENSP00000502432.1	A0A6Q8PGX3

Frequencies

GnomAD3 genomes AF: 0.000221 AC: 12 AN: 54216 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000753

Gnomad EAS AF: 0.000650

Gnomad SAS AF: 0.00139

Gnomad FIN AF: 0.000268

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000117

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000149 AC: 1 AN: 66986 AF XY: 0.0000289

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000141 AC: 16 AN: 1136374 Hom.: 0 Cov.: 37 AF XY: 0.0000145 AC XY: 8 AN XY: 551782

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000417 AC: 1 AN: 23998

American (AMR) AF: 0.00 AC: 0 AN: 23258

Ashkenazi Jewish (ASJ) AF: 0.000124 AC: 2 AN: 16146

East Asian (EAS) AF: 0.0000531 AC: 1 AN: 18828

South Asian (SAS) AF: 0.00 AC: 0 AN: 52300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4246

European-Non Finnish (NFE) AF: 0.0000120 AC: 11 AN: 919460

Other (OTH) AF: 0.0000238 AC: 1 AN: 41980

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000000954792), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000221 AC: 12 AN: 54290 Hom.: 0 Cov.: 0 AF XY: 0.000110 AC XY: 3 AN XY: 27202

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000149 AC: 2 AN: 13392

American (AMR) AF: 0.000326 AC: 2 AN: 6128

Ashkenazi Jewish (ASJ) AF: 0.000753 AC: 1 AN: 1328

East Asian (EAS) AF: 0.000650 AC: 1 AN: 1538

South Asian (SAS) AF: 0.00139 AC: 2 AN: 1440

European-Finnish (FIN) AF: 0.000268 AC: 1 AN: 3726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 78

European-Non Finnish (NFE) AF: 0.000117 AC: 3 AN: 25618

Other (OTH) AF: 0.00 AC: 0 AN: 752

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000162 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.23
DANN	Benign	0.19
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism

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: rs75494928; hg19: chr11-1092420;