Genetic Variant NM_002457.5:c.4239G>A (chr11-1094482-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_002457.5(MUC2):c.4239G>A(p.Thr1413Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC2
NM_002457.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.73

Publications

0 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:

ENSG00000296903 (HGNC:):

ENSG00000296903 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-1094482-G-A is Benign according to our data. Variant chr11-1094482-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2641127.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.73 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002457.5. 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.4239G>A	p.Thr1413Thr	synonymous	Exon 30 of 58	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUC2	ENST00000361558.7	TSL:5	n.4266G>A	non_coding_transcript_exon	Exon 30 of 49
ENSG00000296903	ENST00000743440.1		n.141-161C>T	intron	N/A
MUC2	ENST00000675028.1		c.*57G>A	downstream_gene	N/A	ENSP00000502432.1	A0A6Q8PGX3

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

AN:

53572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00235

Gnomad AMI

AF:

0.00365

Gnomad AMR

AF:

0.000661

Gnomad ASJ

AF:

0.00229

Gnomad EAS

AF:

0.00199

Gnomad SAS

AF:

0.00416

Gnomad FIN

AF:

0.00109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000988

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000134

AC:

AN:

66986

AF XY:

0.000116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000243

Gnomad FIN exome

AF:

0.0000868

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000167

AC:

AN:

1135410

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

551270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23938

American (AMR)

AF:

0.00

AC:

AN:

23176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16108

East Asian (EAS)

AF:

0.0000533

AC:

AN:

18746

South Asian (SAS)

AF:

0.00

AC:

AN:

52280

European-Finnish (FIN)

AF:

0.0000277

AC:

AN:

36156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4246

European-Non Finnish (NFE)

AF:

0.0000174

AC:

AN:

918850

Other (OTH)

AF:

0.0000239

AC:

AN:

41910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00144

AC:

AN:

53636

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

AN XY:

26880

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00234

AC:

AN:

13252

American (AMR)

AF:

0.000660

AC:

AN:

6064

Ashkenazi Jewish (ASJ)

AF:

0.00229

AC:

AN:

1308

East Asian (EAS)

AF:

0.00200

AC:

AN:

1502

South Asian (SAS)

AF:

0.00416

AC:

AN:

1442

European-Finnish (FIN)

AF:

0.00109

AC:

AN:

3674

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000988

AC:

AN:

25306

Other (OTH)

AF:

0.00

AC:

AN:

734

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.245

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000970

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.49

(source)

DANN

Benign

0.19

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over