22-44165407-T-C

Variant names:

• chr22-44165407-T-C
• rs5764106
• NM_013327.5:c.1018+1477T>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.1018+1477T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,040 control chromosomes in the GnomAD database, including 10,158 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 (10158 hom., cov: 33)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_013327.5	c.1018+1477T>C		intron_variant	Intron 12 of 12	ENST00000338758.12	NP_037459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12	c.1018+1477T>C		intron_variant	Intron 12 of 12	1	NM_013327.5	ENSP00000342492.6

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52305 AN: 151922 Hom.: 10118 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.345 AC: 52392 AN: 152040 Hom.: 10158 Cov.: 33 AF XY: 0.351 AC XY: 26073 AN XY: 74332

African (AFR) AF: 0.469 AC: 19451 AN: 41440

American (AMR) AF: 0.261 AC: 3985 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3688 AN: 5162

South Asian (SAS) AF: 0.353 AC: 1702 AN: 4824

European-Finnish (FIN) AF: 0.409 AC: 4318 AN: 10562

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17236 AN: 67976

Other (OTH) AF: 0.337 AC: 711 AN: 2110

Alfa AF: 0.279 Hom.: 12245

Bravo AF: 0.342

Asia WGS AF: 0.522 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.28
PhyloP100		-3.5
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: rs5764106; hg19: chr22-44561287;