rs2306949

chr4-70474006-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

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

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing variant, 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	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC7	NM_152291.3	c.-15-1G>A		splice_acceptor_variant		ENST00000304887.6
MUC7	NM_001145006.2	c.-15-1G>A		splice_acceptor_variant
MUC7	NM_001145007.2	c.-15-1G>A		splice_acceptor_variant
MUC7	XM_047415723.1	c.-15-1G>A		splice_acceptor_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC7	ENST00000304887.6	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.: 31

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

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.: 29 AF XY: 0.162 AC XY: 116953 AN XY: 721482

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.: 31 AF XY: 0.181 AC XY: 13422 AN XY: 74130

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	23
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

Other links and lift over

dbSNP: rs2306949; hg19: chr4-71339723; COSMIC: COSV59218861;