4-70481421-CATCTTCCTCAGCTCCACCAGAGACCACAGCTGCCCCACCCACACCTTCTGCAACTACACCAGCTCCACT-C

Position:

• chr4-70481421-CATCTTCCTCAGCTCCACCAGAGACCACAGCTGCCCCACCCACACCTTCTGCAACTACACCAGCTCCACT-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The ENST00000304887.6(MUC7):​c.710_778del​(p.Ala237_Ala259del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 148,582 control chromosomes in the GnomAD database, including 326 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (326 hom., cov: 23)
  • Exomes 𝑓: 0.026 (2701 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC7 ENST00000304887.6 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.15

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 Benign. Variant got -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in ENST00000304887.6.
• BP6: Variant 4-70481421-CATCTTCCTCAGCTCCACCAGAGACCACAGCTGCCCCACCCACACCTTCTGCAACTACACCAGCTCCACT-C is Benign according to our data. Variant chr4-70481421-CATCTTCCTCAGCTCCACCAGAGACCACAGCTGCCCCACCCACACCTTCTGCAACTACACCAGCTCCACT-C is described in ClinVar as [Benign]. Clinvar id is 777971.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC7	NM_152291.3	c.710_778del	p.Ala237_Ala259del	inframe_deletion	3/3	ENST00000304887.6	NP_689504.2
MUC7	NM_001145006.2	c.710_778del	p.Ala237_Ala259del	inframe_deletion	4/4		NP_001138478.1
MUC7	NM_001145007.2	c.710_778del	p.Ala237_Ala259del	inframe_deletion	4/4		NP_001138479.1
MUC7	XM_047415723.1	c.710_778del	p.Ala237_Ala259del	inframe_deletion	4/4		XP_047271679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC7	ENST00000304887.6	c.710_778del	p.Ala237_Ala259del	inframe_deletion	3/3	1	NM_152291.3	ENSP00000302021	P1
MUC7	ENST00000413702.5	c.710_778del	p.Ala237_Ala259del	inframe_deletion	4/4	4		ENSP00000407422	P1
MUC7	ENST00000456088.5	c.710_778del	p.Ala237_Ala259del	inframe_deletion	4/4	4		ENSP00000400585	P1

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3862 AN: 148472 Hom.: 324 Cov.: 23

Gnomad AFR AF: 0.00968

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0300

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0278

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0256 AC: 37175 AN: 1450788 Hom.: 2701 AF XY: 0.0274 AC XY: 19769 AN XY: 720984

Gnomad4 AFR exome AF: 0.00929

Gnomad4 AMR exome AF: 0.0418

Gnomad4 ASJ exome AF: 0.0960

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.0364

Gnomad4 FIN exome AF: 0.0585

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0336

GnomAD4 genome AF: 0.0261 AC: 3874 AN: 148582 Hom.: 326 Cov.: 23 AF XY: 0.0269 AC XY: 1947 AN XY: 72506

Gnomad4 AFR AF: 0.00982

Gnomad4 AMR AF: 0.0317

Gnomad4 ASJ AF: 0.0891

Gnomad4 EAS AF: 0.0690

Gnomad4 SAS AF: 0.0362

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.0268

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0914 Hom.: 99

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Asthma, protection against Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jul 01, 2006

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1560560839; hg19: chr4-71347138;