Genetic Variant NM_002457.5:c.4335G>T (chr11-1094578-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_002457.5(MUC2):c.4335G>T(p.Thr1445Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 571,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000012 ( 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: -3.20

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-1094578-G-T is Benign according to our data. Variant chr11-1094578-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2641128.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.2 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.4335G>T	p.Thr1445Thr	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.4362G>T	non_coding_transcript_exon	Exon 30 of 49
ENSG00000296903	ENST00000743440.1		n.141-257C>A	intron	N/A
MUC2	ENST00000675028.1		c.*153G>T	downstream_gene	N/A	ENSP00000502432.1	A0A6Q8PGX3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

4986

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

571084

Hom.:

Cov.:

AF XY:

0.00000731

AC XY:

AN XY:

273732

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

12614

American (AMR)

AF:

0.00

AC:

AN:

7928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7024

East Asian (EAS)

AF:

0.00

AC:

AN:

7860

South Asian (SAS)

AF:

0.00

AC:

AN:

26508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1320

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

473260

Other (OTH)

AF:

0.00

AC:

AN:

21502

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000545177), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.368

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: AC0

AF:

0.00

AC:

AN:

4986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

2454

African (AFR)

AF:

0.00

AC:

AN:

1126

American (AMR)

AF:

0.00

AC:

AN:

566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

108

East Asian (EAS)

AF:

0.00

AC:

AN:

142

South Asian (SAS)

AF:

0.00

AC:

AN:

154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

2332

Other (OTH)

AF:

0.00

AC:

AN:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

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

-0.93

CADD

Benign

0.030

(source)

DANN

Benign

0.26

PhyloP100

-3.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over