rs10500758

chr11-12523822-A-Gchr11-12523822-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018222.5(PARVA):c.1043-4027A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 152,308 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.038 (292 hom., cov: 33)
• Consequence: PARVA NM_018222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

Genes affected

PARVA (HGNC:14652): (parvin alpha) This gene encodes a member of the parvin family of actin-binding proteins. Parvins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. The encoded protein is part of the integrin-linked kinase signaling complex and plays a role in cell adhesion, motility and survival. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVA	NM_018222.5	c.1043-4027A>G		intron_variant		ENST00000334956.15
PARVA	XM_005253015.4	c.911-4027A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVA	ENST00000334956.15	c.1043-4027A>G		intron_variant		1	NM_018222.5	P1

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5787 AN: 152190 Hom.: 290 Cov.: 33

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0380 AC: 5786 AN: 152308 Hom.: 292 Cov.: 33 AF XY: 0.0430 AC XY: 3201 AN XY: 74476

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0284

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0250 Hom.: 82

Bravo AF: 0.0390

Asia WGS AF: 0.171 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	10
Dann	Benign	0.75

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

Other links and lift over

dbSNP: rs10500758; hg19: chr11-12545369;