rs2291652

Variant names:

• chr3-195750920-G-A
• rs2291652
• NM_018406.7:c.15840C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-195750920-G-A
• chr3-195750920-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018406.7(MUC4):​c.15840C>T​(p.Ile5280Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,613,572 control chromosomes in the GnomAD database, including 160,084 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 0.37 (12230 hom., cov: 29)
  • Exomes 𝑓: 0.44 (147854 hom.)
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426
• Publications: 48 publications found

Genes affected

MUC4 (HGNC:7514): (mucin 4, cell surface associated) The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.426 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7	c.15840C>T	p.Ile5280Ile	synonymous_variant	Exon 23 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.3132C>T	p.Ile1044Ile	synonymous_variant	Exon 22 of 24		NP_004523.3
MUC4	NM_138297.5	c.2979C>T	p.Ile993Ile	synonymous_variant	Exon 21 of 23		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.15840C>T	p.Ile5280Ile	synonymous_variant	Exon 23 of 25	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55704 AN: 151788 Hom.: 12229 Cov.: 29

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.389

GnomAD2 exomes AF: 0.444 AC: 111580 AN: 251044 AF XY: 0.446

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.429

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.750

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.440

GnomAD4 exome AF: 0.443 AC: 647359 AN: 1461666 Hom.: 147854 Cov.: 68 AF XY: 0.442 AC XY: 321520 AN XY: 727138

African (AFR) AF: 0.116 AC: 3877 AN: 33480

American (AMR) AF: 0.424 AC: 18947 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 11052 AN: 26136

East Asian (EAS) AF: 0.738 AC: 29294 AN: 39700

South Asian (SAS) AF: 0.389 AC: 33512 AN: 86248

European-Finnish (FIN) AF: 0.479 AC: 25539 AN: 53346

Middle Eastern (MID) AF: 0.286 AC: 1627 AN: 5690

European-Non Finnish (NFE) AF: 0.447 AC: 497245 AN: 1111962

Other (OTH) AF: 0.435 AC: 26266 AN: 60386

GnomAD4 genome AF: 0.367 AC: 55722 AN: 151906 Hom.: 12230 Cov.: 29 AF XY: 0.370 AC XY: 27482 AN XY: 74226

African (AFR) AF: 0.131 AC: 5455 AN: 41492

American (AMR) AF: 0.403 AC: 6155 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1437 AN: 3464

East Asian (EAS) AF: 0.747 AC: 3838 AN: 5140

South Asian (SAS) AF: 0.416 AC: 1999 AN: 4804

European-Finnish (FIN) AF: 0.479 AC: 5046 AN: 10540

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30359 AN: 67882

Other (OTH) AF: 0.393 AC: 831 AN: 2112

Alfa AF: 0.422 Hom.: 47283

Bravo AF: 0.351

Asia WGS AF: 0.583 AC: 2025 AN: 3478

EpiCase AF: 0.446

EpiControl AF: 0.453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.9
DANN	Benign	0.64
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291652; hg19: chr3-195477791; COSMIC: COSV57773744;