chr19-45523883-TAG-T

Variant names:

• chr19-45523883-TAG-T
• rs142603528
• NM_003370.4:c.910+9_910+10delAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003370.4(VASP):​c.910+9_910+10delAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,613,290 control chromosomes in the GnomAD database, including 50 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (19 hom., cov: 30)
  • Exomes 𝑓: 0.0011 (31 hom.)
• Consequence: VASP NM_003370.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.869

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]

LOC107985315 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-45523883-TAG-T is Benign according to our data. Variant chr19-45523883-TAG-T is described in ClinVar as [Benign]. Clinvar id is 788022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00998 (1513/151664) while in subpopulation AFR AF = 0.0345 (1428/41354). AF 95% confidence interval is 0.033. There are 19 homozygotes in GnomAd4. There are 688 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 1513 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VASP	NM_003370.4	c.910+9_910+10delAG		intron_variant	Intron 9 of 12	ENST00000245932.11	NP_003361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VASP	ENST00000245932.11	c.910+9_910+10delAG		intron_variant	Intron 9 of 12	1	NM_003370.4	ENSP00000245932.5

Frequencies

GnomAD3 genomes AF: 0.00998 AC: 1513 AN: 151546 Hom.: 19 Cov.: 30

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00395

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00822

GnomAD2 exomes AF: 0.00269 AC: 672 AN: 249728 AF XY: 0.00222

Gnomad AFR exome AF: 0.0361

Gnomad AMR exome AF: 0.00221

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000797

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00111 AC: 1625 AN: 1461626 Hom.: 31 AF XY: 0.000993 AC XY: 722 AN XY: 727110

Gnomad4 AFR exome AF: 0.0383 AC: 1283 AN: 33476

Gnomad4 AMR exome AF: 0.00226 AC: 101 AN: 44688

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26132

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39696

Gnomad4 SAS exome AF: 0.0000580 AC: 5 AN: 86240

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53354

Gnomad4 NFE exome AF: 0.0000657 AC: 73 AN: 1111930

Gnomad4 Remaining exome AF: 0.00262 AC: 158 AN: 60344

GnomAD4 genome AF: 0.00998 AC: 1513 AN: 151664 Hom.: 19 Cov.: 30 AF XY: 0.00929 AC XY: 688 AN XY: 74070

Gnomad4 AFR AF: 0.0345 AC: 0.0345311 AN: 0.0345311

Gnomad4 AMR AF: 0.00394 AC: 0.00394218 AN: 0.00394218

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000118 AC: 0.000117859 AN: 0.000117859

Gnomad4 OTH AF: 0.00813 AC: 0.00813397 AN: 0.00813397

Alfa AF: 0.00447 Hom.: 1

Bravo AF: 0.0109

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142603528; hg19: chr19-46027141;