11-1256664-C-T

Position:

chr11-1256664-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002458.3(MUC5B):c.16137-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,555,898 control chromosomes in the GnomAD database, including 859 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 63 hom., cov: 31)

Exomes 𝑓: 0.030 ( 796 hom. )

Consequence

MUC5B
NM_002458.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008739

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.533

Variant links:

Genes affected

MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]

MUC5B links:

MIR6744 (HGNC:50051): (microRNA 6744) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6744 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 11-1256664-C-T is Benign according to our data. Variant chr11-1256664-C-T is described in ClinVar as [Benign]. Clinvar id is 164008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1256664-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3790/151838) while in subpopulation NFE AF= 0.0327 (2217/67902). AF 95% confidence interval is 0.0315. There are 63 homozygotes in gnomad4. There are 1885 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3790 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.16137-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000529681.5	NP_002449.2
MIR6744	NR_106802.1 linkuse as main transcript	n.60C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.16137-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_002458.3	ENSP00000436812	P1
MIR6744	ENST00000619480.1 linkuse as main transcript	n.60C>T		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3791

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00748

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00790

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0226

GnomAD3 exomes

AF:

0.0253

AC:

4211

AN:

166686

Hom.:

AF XY:

0.0247

AC XY:

2215

AN XY:

89758

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.00531

Gnomad ASJ exome

AF:

0.0274

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00976

Gnomad FIN exome

AF:

0.0730

Gnomad NFE exome

AF:

0.0324

Gnomad OTH exome

AF:

0.0234

GnomAD4 exome

AF:

0.0301

AC:

42234

AN:

1404060

Hom.:

796

Cov.:

AF XY:

0.0294

AC XY:

20390

AN XY:

694028

show subpopulations

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.00565

Gnomad4 ASJ exome

AF:

0.0288

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00965

Gnomad4 FIN exome

AF:

0.0723

Gnomad4 NFE exome

AF:

0.0324

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0250

AC:

3790

AN:

151838

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1885

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.00747

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00791

Gnomad4 FIN

AF:

0.0692

Gnomad4 NFE

AF:

0.0326

Gnomad4 OTH

AF:

0.0224

Alfa

AF:

0.0286

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

16137-7C>T in intron 38 of MUC5B: This variant is not expected to have clinical significance because it has been identified in 3.0% (252/8296) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs56310773). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.7

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00087

dbscSNV1_RF

Benign

0.032

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over