Genetic Variant PDGFRL:c.940-3C>T (chr8-17642610-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001372073.1(PDGFRL):c.940-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,592,496 control chromosomes in the GnomAD database, including 6,827 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.088 ( 693 hom., cov: 32)

Exomes 𝑓: 0.085 ( 6134 hom. )

Consequence

PDGFRL
NM_001372073.1 splice_region, intron

Scores

Splicing: ADA: 0.02309

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60

Variant links:

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]

PDGFRL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRL	NM_001372073.1 link	c.940-3C>T		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000251630.11	NP_001359002.1
PDGFRL	NM_006207.2 link	c.940-3C>T		splice_region_variant, intron_variant	Intron 6 of 6		NP_006198.1	Q15198

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDGFRL	ENST00000251630.11 link	c.940-3C>T	splice_region_variant, intron_variant	Intron 5 of 5	5	NM_001372073.1	ENSP00000251630.4	Q15198
PDGFRL	ENST00000541323.1 link	c.940-3C>T	splice_region_variant, intron_variant	Intron 6 of 6	2		ENSP00000444211.1	Q15198
PDGFRL	ENST00000523248.1 link	n.144-961C>T	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13449

AN:

152072

Hom.:

694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0859

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0662

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0750

Gnomad OTH

AF:

0.0978

GnomAD3 exomes

AF:

0.106

AC:

26472

AN:

250598

Hom.:

1770

AF XY:

0.103

AC XY:

13938

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.0905

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.0671

Gnomad NFE exome

AF:

0.0743

Gnomad OTH exome

AF:

0.0958

GnomAD4 exome

AF:

0.0854

AC:

122946

AN:

1440304

Hom.:

6134

Cov.:

AF XY:

0.0862

AC XY:

61900

AN XY:

718034

show subpopulations

Gnomad4 AFR exome

AF:

0.0872

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.0867

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0673

Gnomad4 NFE exome

AF:

0.0756

Gnomad4 OTH exome

AF:

0.0920

GnomAD4 genome

AF:

0.0884

AC:

13454

AN:

152192

Hom.:

693

Cov.:

AF XY:

0.0902

AC XY:

6715

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0858

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.0662

Gnomad4 NFE

AF:

0.0750

Gnomad4 OTH

AF:

0.0963

Alfa

AF:

0.0708

Hom.:

273

Bravo

AF:

0.0969

Asia WGS

AF:

0.150

AC:

521

AN:

3478

EpiCase

AF:

0.0799

EpiControl

AF:

0.0722

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.023

dbscSNV1_RF

Benign

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over