11-1100037-C-T

Variant names:

• chr11-1100037-C-T
• rs7934606
• NM_002457.5:c.9772+12C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002457.5(MUC2):​c.9772+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,571,102 control chromosomes in the GnomAD database, including 120,318 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 0.30 (8458 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111860 hom.)
• Consequence: MUC2 NM_002457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 37 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC2	NM_002457.5	c.9772+12C>T		intron_variant	Intron 39 of 57		NP_002448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000674892.1	c.256+12C>T		intron_variant	Intron 1 of 19			ENSP00000501871.1
MUC2	ENST00000361558.7	n.9809+12C>T		intron_variant	Intron 30 of 48	5

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46020 AN: 151940 Hom.: 8453 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.00635

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.386 AC: 547104 AN: 1419044 Hom.: 111860 Cov.: 58 AF XY: 0.382 AC XY: 268300 AN XY: 702458

African (AFR) AF: 0.114 AC: 3778 AN: 33104

American (AMR) AF: 0.273 AC: 11670 AN: 42746

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 8317 AN: 23882

East Asian (EAS) AF: 0.00581 AC: 229 AN: 39430

South Asian (SAS) AF: 0.250 AC: 20210 AN: 80984

European-Finnish (FIN) AF: 0.438 AC: 16964 AN: 38752

Middle Eastern (MID) AF: 0.329 AC: 1845 AN: 5610

European-Non Finnish (NFE) AF: 0.423 AC: 462962 AN: 1095498

Other (OTH) AF: 0.358 AC: 21129 AN: 59038

GnomAD4 genome AF: 0.303 AC: 46047 AN: 152058 Hom.: 8458 Cov.: 32 AF XY: 0.303 AC XY: 22492 AN XY: 74350

African (AFR) AF: 0.123 AC: 5103 AN: 41510

American (AMR) AF: 0.292 AC: 4463 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3470

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5182

South Asian (SAS) AF: 0.237 AC: 1144 AN: 4818

European-Finnish (FIN) AF: 0.427 AC: 4512 AN: 10558

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28386 AN: 67944

Other (OTH) AF: 0.307 AC: 645 AN: 2102

Alfa AF: 0.363 Hom.: 20380

Bravo AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
PhyloP100		-0.26
PromoterAI		-0.0034	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7934606; hg19: chr11-1093945;