rs12459358

Positions:

• chr19-9040354-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001414686.1(MUC16):​c.83-4286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,910 control chromosomes in the GnomAD database, including 9,252 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 0.34 (9252 hom., cov: 30)
• Consequence: MUC16 NM_001414686.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

Genes affected

MUC16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC16	NM_001414686.1	c.83-4286G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51310 AN: 151790 Hom.: 9248 Cov.: 30

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.338 AC: 51343 AN: 151910 Hom.: 9252 Cov.: 30 AF XY: 0.337 AC XY: 25033 AN XY: 74224

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.332

Alfa AF: 0.359 Hom.: 910

Bravo AF: 0.340

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.0
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12459358; hg19: chr19-9151030;