rs2179559

Variant names:

• chr22-44134199-G-A
• rs2179559
• NM_013327.5:c.633+1190G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000338758.12(PARVB):​c.633+1190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,160 control chromosomes in the GnomAD database, including 2,569 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 0.17 (2569 hom., cov: 32)
• Consequence: PARVB ENST00000338758.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000338758.12. 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_013327.5	MANE Select	c.633+1190G>A		intron	N/A	NP_037459.2
	PARVB	NM_001003828.3		c.732+1190G>A		intron	N/A	NP_001003828.1
	PARVB	NM_001243385.2		c.522+1190G>A		intron	N/A	NP_001230314.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000338758.12	TSL:1 MANE Select	c.633+1190G>A		intron	N/A	ENSP00000342492.6
	PARVB	ENST00000406477.7	TSL:1	c.732+1190G>A		intron	N/A	ENSP00000384515.3
	PARVB	ENST00000404989.1	TSL:1	c.522+1190G>A		intron	N/A	ENSP00000384353.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26066 AN: 152042 Hom.: 2568 Cov.: 32

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.171 AC: 26086 AN: 152160 Hom.: 2569 Cov.: 32 AF XY: 0.169 AC XY: 12595 AN XY: 74390

African (AFR) AF: 0.0954 AC: 3962 AN: 41534

American (AMR) AF: 0.231 AC: 3533 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3472

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5164

South Asian (SAS) AF: 0.137 AC: 658 AN: 4818

European-Finnish (FIN) AF: 0.214 AC: 2265 AN: 10596

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14361 AN: 67970

Other (OTH) AF: 0.178 AC: 377 AN: 2116

Alfa AF: 0.199 Hom.: 10070

Bravo AF: 0.171

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.21
DANN	Benign	0.68
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2179559; hg19: chr22-44530079;