rs952251

chr11-12428690-G-A

Variant summary

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

The NM_018222.5(PARVA):c.137-45055G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,102 control chromosomes in the GnomAD database, including 14,617 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 0.43 (14617 hom., cov: 32)
• Consequence: PARVA NM_018222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVA	NM_018222.5	c.137-45055G>A		intron_variant		ENST00000334956.15
PARVA	XM_005253015.4	c.5-45055G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVA	ENST00000334956.15	c.137-45055G>A		intron_variant		1	NM_018222.5	P1
PARVA	ENST00000530755.5	n.222-45055G>A		intron_variant, non_coding_transcript_variant		2
PARVA	ENST00000533345.5	n.113+30337G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64869 AN: 151984 Hom.: 14595 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.427 AC: 64933 AN: 152102 Hom.: 14617 Cov.: 32 AF XY: 0.426 AC XY: 31681 AN XY: 74330

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.412

Alfa AF: 0.370 Hom.: 17153

Bravo AF: 0.442

Asia WGS AF: 0.361 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.5
Dann	Benign	0.80

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: rs952251; hg19: chr11-12450237;