rs75617873

Positions:

• chr22-44130225-A-C
• chr22-44130225-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013327.5(PARVB):​c.377-1262A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,344 control chromosomes in the GnomAD database, including 53 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 0.023 (53 hom., cov: 33)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

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=-0.92).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0229 (3486/152344) while in subpopulation AFR AF= 0.0262 (1089/41570). AF 95% confidence interval is 0.025. There are 53 homozygotes in gnomad4. There are 1571 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVB	NM_013327.5	c.377-1262A>C		intron_variant		ENST00000338758.12	NP_037459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12	c.377-1262A>C		intron_variant		1	NM_013327.5	ENSP00000342492	P3

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3481 AN: 152226 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00800

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0229 AC: 3486 AN: 152344 Hom.: 53 Cov.: 33 AF XY: 0.0211 AC XY: 1571 AN XY: 74504

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00800

Gnomad4 NFE AF: 0.0260

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0251 Hom.: 7

Bravo AF: 0.0241

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.43

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: rs75617873; hg19: chr22-44526105;