11-1100449-A-G

Position:

• chr11-1100449-A-G

Variant summary

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

The NM_002457.5(MUC2):​c.9773-308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,116 control chromosomes in the GnomAD database, including 22,094 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 0.52 (22094 hom., cov: 33)
• Consequence: MUC2 NM_002457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.36

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC2	NM_002457.5	c.9773-308A>G		intron_variant		ENST00000713550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC2	ENST00000674892.1	c.257-308A>G		intron_variant				A2
MUC2	ENST00000361558.7	n.9810-308A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79203 AN: 151998 Hom.: 22071 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.0687

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.521 AC: 79273 AN: 152116 Hom.: 22094 Cov.: 33 AF XY: 0.514 AC XY: 38192 AN XY: 74344

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.0691

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.478

Alfa AF: 0.494 Hom.: 14885

Bravo AF: 0.517

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10902089; hg19: chr11-1094357;