19-45518061-G-A

Position:

chr19-45518061-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003370.4(VASP):c.310G>A(p.Ala104Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,613,748 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 36 hom. )

Consequence

VASP
NM_003370.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

VASP (HGNC:12652): (vasodilator stimulated phosphoprotein) Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena-VASP protein family. Ena-VASP family members contain an EHV1 N-terminal domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions. In the mid-region of the protein, family members have a proline-rich domain that binds SH3 and WW domain-containing proteins. Their C-terminal EVH2 domain mediates tetramerization and binds both G and F actin. VASP is associated with filamentous actin formation and likely plays a widespread role in cell adhesion and motility. VASP may also be involved in the intracellular signaling pathways that regulate integrin-extracellular matrix interactions. VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. [provided by RefSeq, Jul 2008]

VASP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003001541).

BP6

Variant 19-45518061-G-A is Benign according to our data. Variant chr19-45518061-G-A is described in ClinVar as [Benign]. Clinvar id is 788021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1723/152362) while in subpopulation AFR AF= 0.0391 (1625/41584). AF 95% confidence interval is 0.0375. There are 27 homozygotes in gnomad4. There are 798 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1723 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VASP	NM_003370.4 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	3/13	ENST00000245932.11	NP_003361.1
VASP	XM_005259199.3 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	3/13		XP_005259256.1
VASP	XM_005259200.3 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	3/13		XP_005259257.1
VASP	XM_017027200.3 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	3/13		XP_016882689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VASP	ENST00000245932.11 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	3/13	1	NM_003370.4	ENSP00000245932	P1

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1723

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0392

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00310

AC:

774

AN:

249564

Hom.:

AF XY:

0.00249

AC XY:

338

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.0409

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000979

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00126

AC:

1835

AN:

1461386

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

814

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.0422

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000755

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.0113

AC:

1723

AN:

152362

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

798

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0391

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00243

Hom.:

Bravo

AF:

0.0125

ESP6500AA

AF:

0.0388

AC:

171

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00374

AC:

454

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.54

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.67

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.62

REVEL

Benign

0.023

Sift

Benign

0.30

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.059

MVP

0.28

MPC

0.33

ClinPred

0.0032

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.38

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.

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