rs2075859

Variant names:

• chr11-1229258-C-T
• rs2075859
• NM_002458.3:c.1065C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1229258-C-T
• chr11-1229258-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002458.3(MUC5B):​c.1065C>T​(p.Cys355Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,586,682 control chromosomes in the GnomAD database, including 109,515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10199 hom., cov: 33)
  • Exomes 𝑓: 0.37 (99316 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.118
• Publications: 32 publications found

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 Gene-Disease associations (from GenCC):

• interstitial lung disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 11-1229258-C-T is Benign according to our data. Variant chr11-1229258-C-T is described in ClinVar as Benign. ClinVar VariationId is 178786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.118 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002458.3. 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
	MUC5B	NM_002458.3	MANE Select	c.1065C>T	p.Cys355Cys	synonymous	Exon 9 of 49	NP_002449.2	Q9HC84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.1065C>T	p.Cys355Cys	synonymous	Exon 9 of 49	ENSP00000436812.1	Q9HC84
	MUC5B	ENST00000525715.5	TSL:1	n.1123C>T		non_coding_transcript_exon	Exon 9 of 26
	MUC5B	ENST00000531082.1	TSL:3	n.335C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54721 AN: 151892 Hom.: 10182 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.371

GnomAD2 exomes AF: 0.387 AC: 81495 AN: 210640 AF XY: 0.380

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.609

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.365

Gnomad OTH exome AF: 0.376

GnomAD4 exome AF: 0.370 AC: 530320 AN: 1434672 Hom.: 99316 Cov.: 49 AF XY: 0.367 AC XY: 261566 AN XY: 712066

African (AFR) AF: 0.282 AC: 9269 AN: 32848

American (AMR) AF: 0.450 AC: 18978 AN: 42132

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8581 AN: 25636

East Asian (EAS) AF: 0.596 AC: 22726 AN: 38146

South Asian (SAS) AF: 0.330 AC: 27297 AN: 82718

European-Finnish (FIN) AF: 0.364 AC: 16668 AN: 45818

Middle Eastern (MID) AF: 0.330 AC: 1893 AN: 5738

European-Non Finnish (NFE) AF: 0.366 AC: 403004 AN: 1102128

Other (OTH) AF: 0.368 AC: 21904 AN: 59508

GnomAD4 genome AF: 0.360 AC: 54771 AN: 152010 Hom.: 10199 Cov.: 33 AF XY: 0.364 AC XY: 27073 AN XY: 74284

African (AFR) AF: 0.292 AC: 12100 AN: 41470

American (AMR) AF: 0.443 AC: 6770 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3102 AN: 5146

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4822

European-Finnish (FIN) AF: 0.376 AC: 3975 AN: 10578

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24722 AN: 67928

Other (OTH) AF: 0.378 AC: 796 AN: 2108

Alfa AF: 0.364 Hom.: 25148

Bravo AF: 0.364

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.53
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs2075859; hg19: chr11-1250488; COSMIC: COSV71590441;