chr4-70481399-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152291.3(MUC7):c.655C>T(p.Pro219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 117,010 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC7
NM_152291.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.50

Publications

5 publications found

Variant links:

Genes affected

MUC7 (HGNC:7518): (mucin 7, secreted) This gene encodes a small salivary mucin, which is thought to play a role in facilitating the clearance of bacteria in the oral cavity and to aid in mastication, speech, and swallowing. The central domain of this glycoprotein contains tandem repeats, each composed of 23 amino acids. This antimicrobial protein has antibacterial and antifungal activity. The most common allele contains 6 repeats, and some alleles may be associated with susceptibility to asthma. Alternatively spliced transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Oct 2014]

MUC7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064270794).

BP6

Variant 4-70481399-C-T is Benign according to our data. Variant chr4-70481399-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3150682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152291.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC7	NM_152291.3	MANE Select	c.655C>T	p.Pro219Ser	missense	Exon 3 of 3	NP_689504.2	Q8TAX7
MUC7	NM_001145006.2		c.655C>T	p.Pro219Ser	missense	Exon 4 of 4	NP_001138478.1	Q8TAX7
MUC7	NM_001145007.2		c.655C>T	p.Pro219Ser	missense	Exon 4 of 4	NP_001138479.1	Q8TAX7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC7	ENST00000304887.6	TSL:1 MANE Select	c.655C>T	p.Pro219Ser	missense	Exon 3 of 3	ENSP00000302021.5	Q8TAX7
MUC7	ENST00000413702.5	TSL:4	c.655C>T	p.Pro219Ser	missense	Exon 4 of 4	ENSP00000407422.1	Q8TAX7
MUC7	ENST00000456088.5	TSL:4	c.655C>T	p.Pro219Ser	missense	Exon 4 of 4	ENSP00000400585.1	Q8TAX7

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

364

AN:

116956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000766

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00467

Gnomad NFE

AF:

0.0000352

Gnomad OTH

AF:

0.00246

GnomAD2 exomes

AF:

0.00000415

AC:

AN:

241052

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000658

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1419724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706118

African (AFR)

AF:

0.00

AC:

AN:

30912

American (AMR)

AF:

0.00

AC:

AN:

43222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24642

East Asian (EAS)

AF:

0.00

AC:

AN:

37968

South Asian (SAS)

AF:

0.00

AC:

AN:

85832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083304

Other (OTH)

AF:

0.00

AC:

AN:

57076

GnomAD4 genome

AF:

0.00313

AC:

366

AN:

117010

Hom.:

Cov.:

AF XY:

0.00343

AC XY:

195

AN XY:

56796

show subpopulations

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

African (AFR)

AF:

0.0119

AC:

344

AN:

28918

American (AMR)

AF:

0.00106

AC:

AN:

11306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2990

East Asian (EAS)

AF:

0.000769

AC:

AN:

3902

South Asian (SAS)

AF:

0.00

AC:

AN:

3418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7110

Middle Eastern (MID)

AF:

0.00515

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.0000352

AC:

AN:

56828

Other (OTH)

AF:

0.00244

AC:

AN:

1642

⚠️ 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: 0.363

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00989

Hom.:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0030

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.40

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

PhyloP100

-4.5

PrimateAI

Benign

0.33

PROVEAN

Benign

0.46

REVEL

Benign

0.035

Sift

Benign

0.98

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.093

MVP

0.17

MPC

0.025

ClinPred

0.035

GERP RS

-3.8

Varity_R

0.016

gMVP

0.037

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