rs17689541

Positions:

• chr8-17613031-A-G

Variant summary

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

The NM_001372073.1(PDGFRL):​c.354-8020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 152,296 control chromosomes in the GnomAD database, including 79 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 0.026 (79 hom., cov: 33)
• Consequence: PDGFRL NM_001372073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

Genes affected

PDGFRL (HGNC:8805): (platelet derived growth factor receptor like) This gene encodes a protein with significant sequence similarity to the ligand binding domain of platelet-derived growth factor receptor beta. Mutations in this gene, or deletion of a chromosomal segment containing this gene, are associated with sporadic hepatocellular carcinomas, colorectal cancers, and non-small cell lung cancers. This suggests this gene product may function as a tumor suppressor. [provided by RefSeq, Jul 2008]

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 = 0.0823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRL	NM_001372073.1	c.354-8020A>G		intron_variant		ENST00000251630.11	NP_001359002.1
PDGFRL	NM_006207.2	c.354-8020A>G		intron_variant			NP_006198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRL	ENST00000251630.11	c.354-8020A>G		intron_variant		5	NM_001372073.1	ENSP00000251630	P1
PDGFRL	ENST00000541323.1	c.354-8020A>G		intron_variant		2		ENSP00000444211	P1
PDGFRL	ENST00000673645.1	c.354-8020A>G		intron_variant				ENSP00000501219

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 3998 AN: 152178 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0886

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0263 AC: 4012 AN: 152296 Hom.: 79 Cov.: 33 AF XY: 0.0272 AC XY: 2025 AN XY: 74466

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.0890

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0214 Hom.: 64

Bravo AF: 0.0307

Asia WGS AF: 0.0570 AC: 196 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	0.79
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs17689541; hg19: chr8-17470540;