chr11-1018167-ATCG-A

Variant names:

• chr11-1018167-ATCG-A
• rs111749447
• NM_005961.3:c.4631_4633delCGA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PM4_Supporting BP6_Moderate

The NM_005961.3(MUC6):​c.4631_4633delCGA​(p.Thr1544del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,315,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0860

Genes affected

MUC6 (HGNC:7517): (mucin 6, oligomeric mucus/gel-forming) This gene encodes a member of the mucin protein family. Mucins are high molecular weight glycoproteins produced by many epithelial tissues. The protein encoded by this gene is secreted and forms an insoluble mucous barrier that protects the gut lumen. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Variant has high frequency in the AMR (0.0103) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).
• PM4: Nonframeshift variant in NON repetitive region in NM_005961.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 11-1018167-ATCG-A is Benign according to our data. Variant chr11-1018167-ATCG-A is described in ClinVar as [Benign]. Clinvar id is 403202.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC6	NM_005961.3	c.4631_4633delCGA	p.Thr1544del	disruptive_inframe_deletion	Exon 31 of 33	ENST00000421673.7	NP_005952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC6	ENST00000421673.7	c.4631_4633delCGA	p.Thr1544del	disruptive_inframe_deletion	Exon 31 of 33	5	NM_005961.3	ENSP00000406861.2

Frequencies

GnomAD3 genomes AF: 0.000190 AC: 20 AN: 105212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000355

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000318

Gnomad SAS AF: 0.000346

Gnomad FIN AF: 0.000141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000992

Gnomad OTH AF: 0.000680

GnomAD2 exomes AF: 0.00195 AC: 200 AN: 102664 AF XY: 0.00241

Gnomad AFR exome AF: 0.000183

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.00364

Gnomad EAS exome AF: 0.00534

Gnomad FIN exome AF: 0.000246

Gnomad NFE exome AF: 0.00110

Gnomad OTH exome AF: 0.000894

GnomAD4 exome AF: 0.00195 AC: 2565 AN: 1315560 Hom.: 0 AF XY: 0.00233 AC XY: 1528 AN XY: 655462

Gnomad4 AFR exome AF: 0.00295 AC: 88 AN: 29880

Gnomad4 AMR exome AF: 0.0112 AC: 422 AN: 37800

Gnomad4 ASJ exome AF: 0.00792 AC: 184 AN: 23242

Gnomad4 EAS exome AF: 0.000262 AC: 10 AN: 38236

Gnomad4 SAS exome AF: 0.00977 AC: 736 AN: 75356

Gnomad4 FIN exome AF: 0.00222 AC: 113 AN: 50978

Gnomad4 NFE exome AF: 0.000891 AC: 891 AN: 999508

Gnomad4 Remaining exome AF: 0.00181 AC: 100 AN: 55322

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000190 AC: 20 AN: 105260 Hom.: 0 Cov.: 33 AF XY: 0.000254 AC XY: 13 AN XY: 51142

Gnomad4 AFR AF: 0.000273 AC: 0.000272756 AN: 0.000272756

Gnomad4 AMR AF: 0.000354 AC: 0.000354045 AN: 0.000354045

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000319 AC: 0.000318674 AN: 0.000318674

Gnomad4 SAS AF: 0.000348 AC: 0.000347705 AN: 0.000347705

Gnomad4 FIN AF: 0.000141 AC: 0.000140607 AN: 0.000140607

Gnomad4 NFE AF: 0.0000992 AC: 0.0000991945 AN: 0.0000991945

Gnomad4 OTH AF: 0.000669 AC: 0.000669344 AN: 0.000669344

⚠️ The allele balance in gnomAD4 Genomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0301 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=90/10	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

Publications

LitVar

Other links and lift over

dbSNP: rs111749447; hg19: chr11-1018167; COSMIC: COSV70135717; COSMIC: COSV70135717;