Genetic Variant MUC2:c.1000+96T>C (chr11-1081883-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000675028.1(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
ENST00000675028.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.786

Publications

7 publications found

Variant links:

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]

MUC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MUC2	NM_002457.5 link	c.1000+96T>C		intron_variant	Intron 7 of 57		NP_002448.5	Q02817A0A3S8TMF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000675028.1 link	c.1000+96T>C		intron_variant	Intron 7 of 29			ENSP00000502432.1		A0A6Q8PGX3
MUC2	ENST00000361558.7 link	n.1027+96T>C		intron_variant	Intron 7 of 48	5

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79784

AN:

151990

Hom.:

21026

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.530

AC:

15913

AN:

30032

American (AMR)

AF:

0.523

AC:

16580

AN:

31714

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

11678

AN:

21840

East Asian (EAS)

AF:

0.465

AC:

16068

AN:

34576

South Asian (SAS)

AF:

0.603

AC:

42799

AN:

70982

European-Finnish (FIN)

AF:

0.550

AC:

19326

AN:

35136

Middle Eastern (MID)

AF:

0.538

AC:

2101

AN:

3902

European-Non Finnish (NFE)

AF:

0.517

AC:

527975

AN:

1020796

Other (OTH)

AF:

0.517

AC:

28056

AN:

54306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

15837

31674

47510

63347

79184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15920

31840

47760

63680

79600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.525

AC:

79888

AN:

152108

Hom.:

21068

Cov.:

AF XY:

0.530

AC XY:

39407

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.540

AC:

22393

AN:

41500

American (AMR)

AF:

0.522

AC:

7985

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1852

AN:

3470

East Asian (EAS)

AF:

0.452

AC:

2333

AN:

5164

South Asian (SAS)

AF:

0.602

AC:

2907

AN:

4828

European-Finnish (FIN)

AF:

0.545

AC:

5771

AN:

10588

Middle Eastern (MID)

AF:

0.565

AC:

165

AN:

292

European-Non Finnish (NFE)

AF:

0.514

AC:

34916

AN:

67948

Other (OTH)

AF:

0.509

AC:

1074

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

2079

4159

6238

8318

10397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.26

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over