NM_018406.7:c.1130C>T

Variant names:

• chr3-195790450-G-A
• rs1104760
• NM_018406.7:c.1130C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018406.7(MUC4):​c.1130C>T​(p.Thr377Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,613,476 control chromosomes in the GnomAD database, including 526,927 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (48996 hom., cov: 32)
  • Exomes 𝑓: 0.81 (477931 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373
• Publications: 44 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5415636E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018406.7. 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
	MUC4	NM_018406.7	MANE Select	c.1130C>T	p.Thr377Ile	missense	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-11995C>T		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-16145C>T		intron	N/A	NP_612154.2	Q99102-12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	ENST00000463781.8	TSL:5 MANE Select	c.1130C>T	p.Thr377Ile	missense	Exon 2 of 25	ENSP00000417498.3	Q99102-1
	MUC4	ENST00000346145.8	TSL:1	c.83-11995C>T		intron	N/A	ENSP00000304207.6	Q99102-13
	MUC4	ENST00000349607.8	TSL:1	c.83-16145C>T		intron	N/A	ENSP00000338109.4	Q99102-12

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121729 AN: 152002 Hom.: 48958 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.822

GnomAD2 exomes AF: 0.775 AC: 193217 AN: 249256 AF XY: 0.775

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.633

Gnomad ASJ exome AF: 0.841

Gnomad EAS exome AF: 0.805

Gnomad FIN exome AF: 0.797

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.807 AC: 1178986 AN: 1461352 Hom.: 477931 Cov.: 64 AF XY: 0.804 AC XY: 584123 AN XY: 726972

African (AFR) AF: 0.815 AC: 27274 AN: 33470

American (AMR) AF: 0.637 AC: 28509 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 22167 AN: 26134

East Asian (EAS) AF: 0.813 AC: 32280 AN: 39696

South Asian (SAS) AF: 0.668 AC: 57618 AN: 86248

European-Finnish (FIN) AF: 0.792 AC: 42282 AN: 53402

Middle Eastern (MID) AF: 0.812 AC: 4683 AN: 5764

European-Non Finnish (NFE) AF: 0.823 AC: 915207 AN: 1111558

Other (OTH) AF: 0.811 AC: 48966 AN: 60358

GnomAD4 genome AF: 0.801 AC: 121817 AN: 152124 Hom.: 48996 Cov.: 32 AF XY: 0.796 AC XY: 59232 AN XY: 74370

African (AFR) AF: 0.815 AC: 33820 AN: 41472

American (AMR) AF: 0.711 AC: 10870 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2934 AN: 3472

East Asian (EAS) AF: 0.802 AC: 4149 AN: 5176

South Asian (SAS) AF: 0.675 AC: 3256 AN: 4826

European-Finnish (FIN) AF: 0.801 AC: 8487 AN: 10592

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55628 AN: 67988

Other (OTH) AF: 0.824 AC: 1740 AN: 2112

Alfa AF: 0.817 Hom.: 164451

Bravo AF: 0.796

TwinsUK AF: 0.827 AC: 3065

ALSPAC AF: 0.824 AC: 3175

ESP6500AA AF: 0.825 AC: 3228

ESP6500EA AF: 0.824 AC: 6826

ExAC AF: 0.780 AC: 94302

Asia WGS AF: 0.807 AC: 2809 AN: 3478

EpiCase AF: 0.833

EpiControl AF: 0.838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.20
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0000015	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.37
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.018
Sift	Benign	1.0	T
Sift4G	Benign	0.35	T
Vest4		0.11
ClinPred		0.015	T
GERP RS		-0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.014
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: rs1104760; hg19: chr3-195517321; COSMIC: COSV62168911;