rs6006615

Variant names:

• chr22-44011719-T-C
• rs6006615
• ENST00000406477.7:c.211+12046T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000406477.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	NM_001003828.3		c.211+12046T>C		intron	N/A	NP_001003828.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000406477.7	TSL:1	c.211+12046T>C		intron	N/A	ENSP00000384515.3

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

African (AFR) AF: 0.155 AC: 6448 AN: 41468

American (AMR) AF: 0.146 AC: 2228 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.0396 AC: 205 AN: 5174

South Asian (SAS) AF: 0.178 AC: 856 AN: 4808

European-Finnish (FIN) AF: 0.135 AC: 1425 AN: 10576

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11886 AN: 67980

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.174 Hom.: 4481

Bravo AF: 0.159

Asia WGS AF: 0.111 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.36
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6006615; hg19: chr22-44407599;