chr22-44171555-A-G

Position:

• chr22-44171555-A-G

Variant summary

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

The NM_013327.5(PARVB):​c.*2877A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,580 control chromosomes in the GnomAD database, including 8,889 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 0.34 (8881 hom., cov: 29)
  • Exomes 𝑓: 0.23 (8 hom.)
• Consequence: PARVB NM_013327.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVB	NM_013327.5	c.*2877A>G		3_prime_UTR_variant	13/13	ENST00000338758.12	NP_037459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12	c.*2877A>G		3_prime_UTR_variant	13/13	1	NM_013327.5	ENSP00000342492.6

Frequencies

GnomAD3 genomes AF: 0.337 AC: 50960 AN: 151242 Hom.: 8872 Cov.: 29

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.234 AC: 52 AN: 222 Hom.: 8 Cov.: 0 AF XY: 0.250 AC XY: 40 AN XY: 160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.154

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.337 AC: 50995 AN: 151358 Hom.: 8881 Cov.: 29 AF XY: 0.332 AC XY: 24492 AN XY: 73880

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.345

Alfa AF: 0.363 Hom.: 19259

Bravo AF: 0.346

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9614207; hg19: chr22-44567435;