12-40437918-C-G

Variant names:

• chr12-40437918-C-G
• rs10784616
• ENST00000454784.10:c.3221-210C>G

Variant summary

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

The ENST00000454784.10(MUC19):​c.3221-210C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,934 control chromosomes in the GnomAD database, including 20,580 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 0.51 (20580 hom., cov: 32)
• Consequence: MUC19 ENST00000454784.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 2 publications found

Genes affected

MUC19 (HGNC:14362): (mucin 19, oligomeric) This gene encodes a member of the gel-forming mucin protein family. Mucin family members are glycoproteins that have tandem repeats which are extensively O-glycosylated. The structural features of mucin proteins are responsible for the gel-like properties of mucus. The encoded protein may be involved in disruption of the ocular surface in Sjogren syndrome. [provided by RefSeq, Apr 2014]

ENSG00000258167 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC19	NM_173600.2	c.3221-210C>G		intron_variant	Intron 27 of 171		NP_775871.2
LOC105369736	XR_007063562.1	n.74+5905G>C		intron_variant	Intron 1 of 4
LOC105369736	XR_944866.1	n.74+5905G>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.3221-210C>G		intron_variant	Intron 27 of 172	5		ENSP00000508949.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77891 AN: 151816 Hom.: 20559 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.513 AC: 77964 AN: 151934 Hom.: 20580 Cov.: 32 AF XY: 0.521 AC XY: 38677 AN XY: 74250

African (AFR) AF: 0.396 AC: 16383 AN: 41404

American (AMR) AF: 0.583 AC: 8909 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2420 AN: 5158

South Asian (SAS) AF: 0.708 AC: 3406 AN: 4812

European-Finnish (FIN) AF: 0.573 AC: 6044 AN: 10548

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37034 AN: 67952

Other (OTH) AF: 0.544 AC: 1146 AN: 2108

Alfa AF: 0.412 Hom.: 1168

Bravo AF: 0.503

Asia WGS AF: 0.571 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.33
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10784616; hg19: chr12-40831720;