rs6006615

Positions:

• chr22-44011719-T-C

Variant summary

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

The ENST00000406477.7(PARVB):​c.211+12046T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,044 control chromosomes in the GnomAD database, including 1,985 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 0.16 (1985 hom., cov: 31)
• Consequence: PARVB ENST00000406477.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

Genes affected

PARVB (HGNC:14653): (parvin beta) This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_001003828.3	c.211+12046T>C		intron_variant
PARVB	XM_024452236.2	c.211+12046T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000406477.7	c.211+12046T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24293 AN: 151926 Hom.: 1982 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.160 AC: 24294 AN: 152044 Hom.: 1985 Cov.: 31 AF XY: 0.157 AC XY: 11695 AN XY: 74332

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.173

Alfa AF: 0.176 Hom.: 3276

Bravo AF: 0.159

Asia WGS AF: 0.111 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6006615; hg19: chr22-44407599;