chr3-195764168-C-T

Variant names:

• chr3-195764168-C-T
• rs189235965
• NM_018406.7:c.13925-4G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018406.7(MUC4):​c.13925-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,561,516 control chromosomes in the GnomAD database, including 1 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: MUC4 NM_018406.7 splice_region, intron
• Scores: Splicing: ADA: 0.00001424
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-195764168-C-T is Benign according to our data. Variant chr3-195764168-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 760451.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7	c.13925-4G>A		splice_region_variant, intron_variant	Intron 10 of 24	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.1217-4G>A		splice_region_variant, intron_variant	Intron 9 of 23		NP_004523.3
MUC4	NM_138297.5	c.1064-4G>A		splice_region_variant, intron_variant	Intron 8 of 22		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.13925-4G>A		splice_region_variant, intron_variant	Intron 10 of 24	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000450 AC: 74 AN: 164344 AF XY: 0.000526

Gnomad AFR exome AF: 0.000108

Gnomad AMR exome AF: 0.000273

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000770

Gnomad OTH exome AF: 0.000437

GnomAD4 exome AF: 0.000373 AC: 525 AN: 1409238 Hom.: 1 Cov.: 34 AF XY: 0.000383 AC XY: 267 AN XY: 696284

Gnomad4 AFR exome AF: 0.000125 AC: 4 AN: 32122

Gnomad4 AMR exome AF: 0.000244 AC: 9 AN: 36852

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25256

Gnomad4 EAS exome AF: 0.0000548 AC: 2 AN: 36518

Gnomad4 SAS exome AF: 0.000474 AC: 38 AN: 80136

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 49302

Gnomad4 NFE exome AF: 0.000427 AC: 463 AN: 1085058

Gnomad4 Remaining exome AF: 0.000154 AC: 9 AN: 58362

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74446

Gnomad4 AFR AF: 0.0000722 AC: 0.0000722022 AN: 0.0000722022

Gnomad4 AMR AF: 0.000196 AC: 0.000196207 AN: 0.000196207

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000193 AC: 0.00019305 AN: 0.00019305

Gnomad4 SAS AF: 0.000207 AC: 0.000207383 AN: 0.000207383

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000603 AC: 0.000602693 AN: 0.000602693

Gnomad4 OTH AF: 0.000474 AC: 0.000473934 AN: 0.000473934

Alfa AF: 0.000351 Hom.: 0

Bravo AF: 0.000257

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.43
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs189235965; hg19: chr3-195491039;