chr8-17642610-C-T

Variant names:

• chr8-17642610-C-T
• rs17633132
• NM_001372073.1:c.940-3C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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	c.940-3C>T		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000251630.11	NP_001359002.1
PDGFRL	NM_006207.2	c.940-3C>T		splice_region_variant, intron_variant	Intron 6 of 6		NP_006198.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13449 AN: 152072 Hom.: 694 Cov.: 32

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

GnomAD2 exomes AF: 0.106 AC: 26472 AN: 250598 AF XY: 0.103

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 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.: 28 AF XY: 0.0862 AC XY: 61900 AN XY: 718034

African (AFR) AF: 0.0872 AC: 2886 AN: 33082

American (AMR) AF: 0.202 AC: 9002 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 2255 AN: 26010

East Asian (EAS) AF: 0.136 AC: 5386 AN: 39568

South Asian (SAS) AF: 0.132 AC: 11275 AN: 85726

European-Finnish (FIN) AF: 0.0673 AC: 3593 AN: 53390

Middle Eastern (MID) AF: 0.0882 AC: 497 AN: 5638

European-Non Finnish (NFE) AF: 0.0756 AC: 82565 AN: 1092636

Other (OTH) AF: 0.0920 AC: 5487 AN: 59650

GnomAD4 genome AF: 0.0884 AC: 13454 AN: 152192 Hom.: 693 Cov.: 32 AF XY: 0.0902 AC XY: 6715 AN XY: 74408

African (AFR) AF: 0.0858 AC: 3565 AN: 41526

American (AMR) AF: 0.148 AC: 2266 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3472

East Asian (EAS) AF: 0.128 AC: 658 AN: 5154

South Asian (SAS) AF: 0.132 AC: 636 AN: 4816

European-Finnish (FIN) AF: 0.0662 AC: 702 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0750 AC: 5102 AN: 68018

Other (OTH) AF: 0.0963 AC: 203 AN: 2108

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	12
DANN	Benign	0.93
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17633132; hg19: chr8-17500119; COSMIC: COSV50577283; COSMIC: COSV50577283;