rs11602663

Positions:

• chr11-1020778-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005961.3(MUC6):​c.3590-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,602,844 control chromosomes in the GnomAD database, including 25,988 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1696 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24292 hom.)
• Consequence: MUC6 NM_005961.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC6	NM_005961.3	c.3590-44G>A		intron_variant		ENST00000421673.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC6	ENST00000421673.7	c.3590-44G>A		intron_variant		5	NM_005961.3	P1
MUC6	ENST00000527242.2			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20380 AN: 152056 Hom.: 1691 Cov.: 33

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0234

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.146 AC: 35209 AN: 241890 Hom.: 3095 AF XY: 0.149 AC XY: 19644 AN XY: 131540

Gnomad AFR exome AF: 0.0324

Gnomad AMR exome AF: 0.0986

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.0241

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.176 AC: 255785 AN: 1450670 Hom.: 24292 Cov.: 34 AF XY: 0.175 AC XY: 126061 AN XY: 720938

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.0166

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.134 AC: 20392 AN: 152174 Hom.: 1696 Cov.: 33 AF XY: 0.132 AC XY: 9828 AN XY: 74384

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0232

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.155

Alfa AF: 0.165 Hom.: 494

Bravo AF: 0.126

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs11602663; hg19: chr11-1020778; COSMIC: COSV70142943; COSMIC: COSV70142943;