NM_002457.5:c.4239G>C

Variant names:

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

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>C​(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 0.0011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00024 (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=-0.83).
• 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>C	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>C		non_coding_transcript_exon	Exon 30 of 49
	ENSG00000296903	ENST00000743440.1		n.141-161C>G		intron	N/A
	MUC2	ENST00000675028.1		c.*57G>C		downstream_gene	N/A	ENSP00000502432.1	A0A6Q8PGX3

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 60 AN: 54214 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000818

Gnomad ASJ AF: 0.000752

Gnomad EAS AF: 0.000642

Gnomad SAS AF: 0.00137

Gnomad FIN AF: 0.00107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.00136

GnomAD2 exomes AF: 0.00355 AC: 238 AN: 66986 AF XY: 0.00379

Gnomad AFR exome AF: 0.00762

Gnomad AMR exome AF: 0.00294

Gnomad ASJ exome AF: 0.00194

Gnomad EAS exome AF: 0.0112

Gnomad FIN exome AF: 0.000521

Gnomad NFE exome AF: 0.00371

Gnomad OTH exome AF: 0.00620

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000239 AC: 270 AN: 1129806 Hom.: 0 Cov.: 37 AF XY: 0.000272 AC XY: 149 AN XY: 548444

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

African (AFR) AF: 0.00106 AC: 25 AN: 23612

American (AMR) AF: 0.000529 AC: 12 AN: 22664

Ashkenazi Jewish (ASJ) AF: 0.000565 AC: 9 AN: 15924

East Asian (EAS) AF: 0.00232 AC: 42 AN: 18096

South Asian (SAS) AF: 0.000504 AC: 26 AN: 51560

European-Finnish (FIN) AF: 0.0000555 AC: 2 AN: 36048

Middle Eastern (MID) AF: 0.000237 AC: 1 AN: 4214

European-Non Finnish (NFE) AF: 0.000159 AC: 146 AN: 916016

Other (OTH) AF: 0.000168 AC: 7 AN: 41672

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00111 AC: 60 AN: 54288 Hom.: 0 Cov.: 0 AF XY: 0.00140 AC XY: 38 AN XY: 27190

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

African (AFR) AF: 0.00112 AC: 15 AN: 13420

American (AMR) AF: 0.000816 AC: 5 AN: 6130

Ashkenazi Jewish (ASJ) AF: 0.000752 AC: 1 AN: 1330

East Asian (EAS) AF: 0.000642 AC: 1 AN: 1558

South Asian (SAS) AF: 0.00137 AC: 2 AN: 1462

European-Finnish (FIN) AF: 0.00107 AC: 4 AN: 3728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 82

European-Non Finnish (NFE) AF: 0.00121 AC: 31 AN: 25546

Other (OTH) AF: 0.00133 AC: 1 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: 0.00342 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.24
DANN	Benign	0.21
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;