22-44127670-G-C

Variant names:

• chr22-44127670-G-C
• rs133914
• NM_013327.5:c.377-3817G>C

Variant summary

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

The NM_013327.5(PARVB):​c.377-3817G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,878 control chromosomes in the GnomAD database, including 15,038 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 0.44 (15038 hom., cov: 32)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013327.5. 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.377-3817G>C		intron	N/A	NP_037459.2
	PARVB	NM_001003828.3		c.476-3817G>C		intron	N/A	NP_001003828.1
	PARVB	NM_001243385.2		c.266-3817G>C		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.377-3817G>C		intron	N/A	ENSP00000342492.6
	PARVB	ENST00000406477.7	TSL:1	c.476-3817G>C		intron	N/A	ENSP00000384515.3
	PARVB	ENST00000404989.1	TSL:1	c.266-3817G>C		intron	N/A	ENSP00000384353.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66176 AN: 151760 Hom.: 15027 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.436 AC: 66218 AN: 151878 Hom.: 15038 Cov.: 32 AF XY: 0.428 AC XY: 31753 AN XY: 74220

African (AFR) AF: 0.505 AC: 20899 AN: 41410

American (AMR) AF: 0.470 AC: 7179 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1126 AN: 3470

East Asian (EAS) AF: 0.121 AC: 626 AN: 5166

South Asian (SAS) AF: 0.243 AC: 1168 AN: 4810

European-Finnish (FIN) AF: 0.352 AC: 3709 AN: 10524

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30242 AN: 67924

Other (OTH) AF: 0.411 AC: 866 AN: 2108

Alfa AF: 0.451 Hom.: 1929

Bravo AF: 0.450

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.43
PhyloP100		0.18
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: rs133914; hg19: chr22-44523550;