chr4-70474042-T-G

Variant names:

• chr4-70474042-T-G
• rs1431943560
• NM_152291.3:c.21T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152291.3(MUC7):​c.21T>G​(p.Phe7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MUC7 NM_152291.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.586
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043484896).
• BP6: Variant 4-70474042-T-G is Benign according to our data. Variant chr4-70474042-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2518233.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC7	NM_152291.3	MANE Select	c.21T>G	p.Phe7Leu	missense	Exon 2 of 3	NP_689504.2	Q8TAX7
	MUC7	NM_001145006.2		c.21T>G	p.Phe7Leu	missense	Exon 3 of 4	NP_001138478.1	Q8TAX7
	MUC7	NM_001145007.2		c.21T>G	p.Phe7Leu	missense	Exon 3 of 4	NP_001138479.1	Q8TAX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC7	ENST00000304887.6	TSL:1 MANE Select	c.21T>G	p.Phe7Leu	missense	Exon 2 of 3	ENSP00000302021.5	Q8TAX7
	MUC7	ENST00000504482.1	TSL:1	n.315T>G		non_coding_transcript_exon	Exon 2 of 3
	MUC7	ENST00000413702.5	TSL:4	c.21T>G	p.Phe7Leu	missense	Exon 3 of 4	ENSP00000407422.1	Q8TAX7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250936 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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 AF: 0.00000616 AC: 9 AN: 1461084 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726806

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111522

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.064
DANN	Benign	0.78
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.59
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.026
Sift	Benign	0.26	T
Sift4G	Benign	0.58	T
Polyphen		0.0060	B
Vest4		0.33
MutPred		0.33		Loss of ubiquitination at K2 (P = 0.1372)
MVP		0.34
MPC		0.028
ClinPred		0.034	T
GERP RS		-6.2
Varity_R		0.025
gMVP		0.070
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1431943560; hg19: chr4-71339759;