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GeneBe

8-17589661-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001372073.1(PDGFRL):c.249C>A(p.Thr83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,613,248 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 40 hom., cov: 31)
Exomes 𝑓: 0.0011 ( 34 hom. )

Consequence

PDGFRL
NM_001372073.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.273
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-17589661-C-A is Benign according to our data. Variant chr8-17589661-C-A is described in ClinVar as [Benign]. Clinvar id is 714376.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.273 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1652/152248) while in subpopulation AFR AF= 0.0381 (1580/41522). AF 95% confidence interval is 0.0365. There are 40 homozygotes in gnomad4. There are 732 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 39 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDGFRLNM_001372073.1 linkuse as main transcriptc.249C>A p.Thr83= synonymous_variant 2/6 ENST00000251630.11
PDGFRLNM_006207.2 linkuse as main transcriptc.249C>A p.Thr83= synonymous_variant 3/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDGFRLENST00000251630.11 linkuse as main transcriptc.249C>A p.Thr83= synonymous_variant 2/65 NM_001372073.1 P1
PDGFRLENST00000541323.1 linkuse as main transcriptc.249C>A p.Thr83= synonymous_variant 3/72 P1
PDGFRLENST00000673645.1 linkuse as main transcriptc.249C>A p.Thr83= synonymous_variant 3/4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0108
AC:
1649
AN:
152130
Hom.:
39
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0381
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00294
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00283
AC:
711
AN:
251362
Hom.:
12
AF XY:
0.00214
AC XY:
291
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.0389
Gnomad AMR exome
AF:
0.00179
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00114
AC:
1672
AN:
1461000
Hom.:
34
Cov.:
31
AF XY:
0.000993
AC XY:
722
AN XY:
726846
show subpopulations
Gnomad4 AFR exome
AF:
0.0409
Gnomad4 AMR exome
AF:
0.00201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000666
Gnomad4 OTH exome
AF:
0.00212
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0109
AC:
1652
AN:
152248
Hom.:
40
Cov.:
31
AF XY:
0.00983
AC XY:
732
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0381
Gnomad4 AMR
AF:
0.00294
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00711
Alfa
AF:
0.00428
Hom.:
4
Bravo
AF:
0.0122
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.23
Cadd
Benign
2.4
Dann
Benign
0.61

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

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

Other links and lift over

dbSNP: rs61733860; hg19: chr8-17447170; API