rs225918

Positions:

• chr14-29974448-G-A

Variant summary

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

The ENST00000549360.1(ENSG00000248975):​n.204-1215C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,942 control chromosomes in the GnomAD database, including 35,865 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 0.67 (35865 hom., cov: 32)
• Consequence: ENST00000549360.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

Genes affected

(HGNC:):

PRKD1 (HGNC:9407): (protein kinase D1) The protein encoded by this gene is a serine/threonine protein kinase involved in many cellular processes, including Golgi body membrane integrity and transport, cell migration and differentiation, MAPK8/JNK1 and Ras pathway signaling, MAPK1/3 (ERK1/2) pathway signaling, cell survival, and regulation of cell shape and adhesion. [provided by RefSeq, Jan 2017]

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 (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000549360.1	n.204-1215C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000553082.1	n.446-5389G>A		intron_variant, non_coding_transcript_variant		3
PRKD1	ENST00000549503.1	c.33+73262C>T		intron_variant		3		ENSP00000446866
	ENST00000548124.1	n.106+5701C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101550 AN: 151824 Hom.: 35860 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.669 AC: 101581 AN: 151942 Hom.: 35865 Cov.: 32 AF XY: 0.673 AC XY: 50030 AN XY: 74298

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.669

Alfa AF: 0.744 Hom.: 18891

Bravo AF: 0.652

Asia WGS AF: 0.697 AC: 2426 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	0.64
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs225918; hg19: chr14-30443654;