18-1604959-T-C

Variant names:

• chr18-1604959-T-C
• rs12604976
• ENST00000583163.2:n.336-21280T>C

Variant summary

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

The ENST00000583163.2(ENSG00000266602):​n.336-21280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,914 control chromosomes in the GnomAD database, including 11,659 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 0.38 (11659 hom., cov: 31)
• Consequence: ENSG00000266602 ENST00000583163.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130

Genes affected

ENSG00000266602 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000266602	ENST00000583163.2	n.336-21280T>C		intron_variant	Intron 3 of 4	2
ENSG00000266602	ENST00000652957.1	n.251+38435T>C		intron_variant	Intron 2 of 2
ENSG00000266602	ENST00000653006.1	n.312-21280T>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57075 AN: 151796 Hom.: 11638 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.376 AC: 57144 AN: 151914 Hom.: 11659 Cov.: 31 AF XY: 0.383 AC XY: 28435 AN XY: 74256

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.381

Alfa AF: 0.301 Hom.: 7217

Bravo AF: 0.386

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12604976; hg19: chr18-1604960;