Variant rs2306949 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The NM_152291.3(MUC7):c.-15-1G>A variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,601,096 control chromosomes in the GnomAD database, including 23,406 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2913 hom., cov: 31)

Exomes 𝑓: 0.16 ( 20493 hom. )

Consequence

MUC7
NM_152291.3 splice_acceptor

Scores

Splicing: ADA: 0.9998

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.187

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.059964728 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.3, offset of 1, new splice context is: acatttctgcttttcccaAGaga. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MUC7	NM_152291.3 linkuse as main transcript	c.-15-1G>A	splice_acceptor_variant	ENST00000304887.6
MUC7	NM_001145006.2 linkuse as main transcript	c.-15-1G>A	splice_acceptor_variant
MUC7	NM_001145007.2 linkuse as main transcript	c.-15-1G>A	splice_acceptor_variant
MUC7	XM_047415723.1 linkuse as main transcript	c.-15-1G>A	splice_acceptor_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC7	ENST00000304887.6 linkuse as main transcript	c.-15-1G>A		splice_acceptor_variant		1	NM_152291.3	P1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27962

AN:

151604

Hom.:

2907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0827

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.162

AC:

40466

AN:

250348

Hom.:

3605

AF XY:

0.162

AC XY:

21946

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.0946

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.162

AC:

234453

AN:

1449374

Hom.:

20493

Cov.:

AF XY:

0.162

AC XY:

116953

AN XY:

721482

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.0950

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.184

AC:

27985

AN:

151722

Hom.:

2913

Cov.:

AF XY:

0.181

AC XY:

13422

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.0827

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.160

Hom.:

3141

Bravo

AF:

0.186

Asia WGS

AF:

0.186

AC:

650

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.87

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.86

Position offset: 2

DS_AL_spliceai

1.0

Position offset: 1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over