Variant X-15355260-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004469.5(VEGFD):c.531A>G(p.Glu177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,199,097 control chromosomes in the GnomAD database, including 36 homozygotes. There are 600 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 21 hom., 300 hem., cov: 22)

Exomes 𝑓: 0.0012 ( 15 hom. 300 hem. )

Consequence

VEGFD
NM_004469.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.453

Variant links:

Genes affected

VEGFD (HGNC:3708): (vascular endothelial growth factor D) The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family and is active in angiogenesis, lymphangiogenesis, and endothelial cell growth. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms which bind and activate VEGFR-2 and VEGFR-3 receptors. This protein is structurally and functionally similar to vascular endothelial growth factor C. Read-through transcription has been observed between this locus and the upstream PIR (GeneID 8544) locus. [provided by RefSeq, Feb 2011]

VEGFD links:

PIR-FIGF (HGNC:):

PIR-FIGF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-15355260-T-C is Benign according to our data. Variant chrX-15355260-T-C is described in ClinVar as [Benign]. Clinvar id is 778978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.453 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1227/112000) while in subpopulation AFR AF= 0.0373 (1151/30877). AF 95% confidence interval is 0.0355. There are 21 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFD	NM_004469.5 linkuse as main transcript	c.531A>G	p.Glu177=	synonymous_variant	4/7	ENST00000297904.4
PIR-FIGF	NR_037859.2 linkuse as main transcript	n.1506A>G		non_coding_transcript_exon_variant	12/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFD	ENST00000297904.4 linkuse as main transcript	c.531A>G	p.Glu177=	synonymous_variant	4/7	1	NM_004469.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1223

AN:

111949

Hom.:

Cov.:

AF XY:

0.00880

AC XY:

300

AN XY:

34097

show subpopulations

Gnomad AFR

AF:

0.0372

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00397

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00334

AC:

574

AN:

171664

Hom.:

AF XY:

0.00172

AC XY:

AN XY:

57688

show subpopulations

Gnomad AFR exome

AF:

0.0394

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.000275

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000183

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000715

GnomAD4 exome

AF:

0.00117

AC:

1270

AN:

1087097

Hom.:

Cov.:

AF XY:

0.000847

AC XY:

300

AN XY:

354135

show subpopulations

Gnomad4 AFR exome

AF:

0.0387

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000157

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000573

Gnomad4 OTH exome

AF:

0.00236

GnomAD4 genome

AF:

0.0110

AC:

1227

AN:

112000

Hom.:

Cov.:

AF XY:

0.00878

AC XY:

300

AN XY:

34158

show subpopulations

Gnomad4 AFR

AF:

0.0373

Gnomad4 AMR

AF:

0.00397

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000207

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.0123

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.3

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over