ENST00000675028.1:c.2219+45A>G

Variant names:

• chr11-1085368-A-G
• rs7396030
• NM_002457.5:c.2219+45A>G

Variant summary

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

The ENST00000675028.1(MUC2):​c.2219+45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 1,568,748 control chromosomes in the GnomAD database, including 462,936 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 0.71 (38734 hom., cov: 29)
  • Exomes 𝑓: 0.77 (424202 hom.)
• Consequence: MUC2 ENST00000675028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 20 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000675028.1. 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.2219+45A>G		intron	N/A	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000675028.1		c.2219+45A>G		intron	N/A	ENSP00000502432.1	A0A6Q8PGX3
	MUC2	ENST00000361558.7	TSL:5	n.2246+45A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107045 AN: 151458 Hom.: 38729 Cov.: 29

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.770 AC: 1091318 AN: 1417176 Hom.: 424202 Cov.: 27 AF XY: 0.768 AC XY: 540051 AN XY: 703444

African (AFR) AF: 0.560 AC: 18369 AN: 32822

American (AMR) AF: 0.617 AC: 26579 AN: 43100

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 21012 AN: 24922

East Asian (EAS) AF: 0.580 AC: 22732 AN: 39220

South Asian (SAS) AF: 0.635 AC: 52550 AN: 82770

European-Finnish (FIN) AF: 0.762 AC: 33011 AN: 43310

Middle Eastern (MID) AF: 0.783 AC: 4198 AN: 5364

European-Non Finnish (NFE) AF: 0.799 AC: 868223 AN: 1086940

Other (OTH) AF: 0.760 AC: 44644 AN: 58728

GnomAD4 genome AF: 0.707 AC: 107094 AN: 151572 Hom.: 38734 Cov.: 29 AF XY: 0.703 AC XY: 52023 AN XY: 74034

African (AFR) AF: 0.560 AC: 23075 AN: 41242

American (AMR) AF: 0.667 AC: 10181 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2949 AN: 3466

East Asian (EAS) AF: 0.578 AC: 2943 AN: 5094

South Asian (SAS) AF: 0.635 AC: 3044 AN: 4790

European-Finnish (FIN) AF: 0.768 AC: 8090 AN: 10538

Middle Eastern (MID) AF: 0.805 AC: 235 AN: 292

European-Non Finnish (NFE) AF: 0.799 AC: 54268 AN: 67886

Other (OTH) AF: 0.725 AC: 1523 AN: 2100

Alfa AF: 0.775 Hom.: 105680

Bravo AF: 0.693

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs7396030; hg19: chr11-1083364;