rs7127117

Positions:

• chr11-1081883-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002457.5(MUC2):​c.1000+96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,455,392 control chromosomes in the GnomAD database, including 199,599 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 0.53 (21068 hom., cov: 35)
  • Exomes 𝑓: 0.52 (178531 hom.)
• Consequence: MUC2 NM_002457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC2	NM_002457.5	c.1000+96T>C		intron_variant		ENST00000713550.1	NP_002448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000675028.1	c.1000+96T>C		intron_variant				ENSP00000502432	P3
MUC2	ENST00000361558.7	n.1027+96T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79784 AN: 151990 Hom.: 21026 Cov.: 35

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.522 AC: 680496 AN: 1303284 Hom.: 178531 AF XY: 0.524 AC XY: 332374 AN XY: 634548

Gnomad4 AFR exome AF: 0.530

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.525 AC: 79888 AN: 152108 Hom.: 21068 Cov.: 35 AF XY: 0.530 AC XY: 39407 AN XY: 74362

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.509

Alfa AF: 0.685 Hom.: 7390

Bravo AF: 0.520

Asia WGS AF: 0.513 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs7127117; hg19: chr11-1079879;