rs6006636

Variant names:

• chr22-44071872-A-G
• rs6006636
• NM_013327.5:c.113-22056A>G

Variant summary

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

The NM_013327.5(PARVB):​c.113-22056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,130 control chromosomes in the GnomAD database, including 4,253 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 0.21 (4253 hom., cov: 33)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_013327.5	c.113-22056A>G		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.113-22056A>G		intron_variant	Intron 1 of 12	1	NM_013327.5	ENSP00000342492.6

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31924 AN: 152012 Hom.: 4234 Cov.: 33

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.210 AC: 31987 AN: 152130 Hom.: 4253 Cov.: 33 AF XY: 0.205 AC XY: 15277 AN XY: 74384

African (AFR) AF: 0.373 AC: 15482 AN: 41464

American (AMR) AF: 0.174 AC: 2663 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3470

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5176

South Asian (SAS) AF: 0.0957 AC: 461 AN: 4818

European-Finnish (FIN) AF: 0.143 AC: 1512 AN: 10594

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10723 AN: 67992

Other (OTH) AF: 0.204 AC: 432 AN: 2116

Alfa AF: 0.174 Hom.: 4367

Bravo AF: 0.221

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.43
PhyloP100		0.14
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: rs6006636; hg19: chr22-44467752;