22-44039672-G-A

Variant names:

• chr22-44039672-G-A
• rs5764066
• NM_013327.5:c.112+15221G>A

Variant summary

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

The NM_013327.5(PARVB):​c.112+15221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,120 control chromosomes in the GnomAD database, including 8,837 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 0.30 (8837 hom., cov: 32)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_013327.5	c.112+15221G>A		intron_variant	Intron 1 of 12	ENST00000338758.12	NP_037459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12	c.112+15221G>A		intron_variant	Intron 1 of 12	1	NM_013327.5	ENSP00000342492.6

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46304 AN: 152002 Hom.: 8816 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.305 AC: 46357 AN: 152120 Hom.: 8837 Cov.: 32 AF XY: 0.300 AC XY: 22331 AN XY: 74360

African (AFR) AF: 0.543 AC: 22537 AN: 41476

American (AMR) AF: 0.231 AC: 3534 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1169 AN: 5172

South Asian (SAS) AF: 0.259 AC: 1245 AN: 4816

European-Finnish (FIN) AF: 0.188 AC: 1988 AN: 10590

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13860 AN: 68002

Other (OTH) AF: 0.278 AC: 586 AN: 2110

Alfa AF: 0.240 Hom.: 23187

Bravo AF: 0.320

Asia WGS AF: 0.223 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		0.27
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: rs5764066; hg19: chr22-44435552;