Genetic Variant NM_005961.3:c.3590-44G>A (chr11-1020778-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.647

Publications

6 publications found

Variant links:

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]

MUC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MUC6	NM_005961.3 link	c.3590-44G>A		intron_variant	Intron 27 of 32	ENST00000421673.7	NP_005952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC6	ENST00000421673.7 link	c.3590-44G>A		intron_variant	Intron 27 of 32	5	NM_005961.3	ENSP00000406861.2		Q6W4X9
MUC6	ENST00000527242.2 link	c.-46G>A		upstream_gene_variant		3		ENSP00000436903.2		H0YEZ6

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20380

AN:

152056

Hom.:

1691

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.146

AC:

35209

AN:

241890

AF XY:

0.149

show subpopulations

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 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.:

AF XY:

0.175

AC XY:

126061

AN XY:

720938

show subpopulations

African (AFR)

AF:

0.0330

AC:

1101

AN:

33390

American (AMR)

AF:

0.102

AC:

4538

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

3927

AN:

25816

East Asian (EAS)

AF:

0.0166

AC:

657

AN:

39588

South Asian (SAS)

AF:

0.115

AC:

9819

AN:

85640

European-Finnish (FIN)

AF:

0.177

AC:

8654

AN:

49008

Middle Eastern (MID)

AF:

0.177

AC:

995

AN:

5610

European-Non Finnish (NFE)

AF:

0.195

AC:

216015

AN:

1107100

Other (OTH)

AF:

0.168

AC:

10079

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

11353

22706

34059

45412

56765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7354

14708

22062

29416

36770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.134

AC:

20392

AN:

152174

Hom.:

1696

Cov.:

AF XY:

0.132

AC XY:

9828

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0389

AC:

1615

AN:

41546

American (AMR)

AF:

0.131

AC:

2007

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

520

AN:

3472

East Asian (EAS)

AF:

0.0232

AC:

120

AN:

5166

South Asian (SAS)

AF:

0.116

AC:

558

AN:

4818

European-Finnish (FIN)

AF:

0.179

AC:

1899

AN:

10602

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13132

AN:

67954

Other (OTH)

AF:

0.155

AC:

329

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

888

1775

2663

3550

4438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.158

Hom.:

810

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

(source)

DANN

Benign

0.79

PhyloP100

0.65

PromoterAI

0.00060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over