22-44002644-A-G

Variant names:

• chr22-44002644-A-G
• rs5764455
• ENST00000406477.7:c.211+2971A>G

Variant summary

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

The ENST00000406477.7(PARVB):​c.211+2971A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,960 control chromosomes in the GnomAD database, including 26,718 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 0.59 (26718 hom., cov: 31)
• Consequence: PARVB ENST00000406477.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 17 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]

SAMM50 (HGNC:24276): (SAMM50 sorting and assembly machinery component) This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.[provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000406477.7. 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_001003828.3		c.211+2971A>G		intron	N/A	NP_001003828.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000406477.7	TSL:1	c.211+2971A>G		intron	N/A	ENSP00000384515.3
	SAMM50	ENST00000465768.1	TSL:3	n.80-6833A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89652 AN: 151840 Hom.: 26670 Cov.: 31

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.591 AC: 89753 AN: 151960 Hom.: 26718 Cov.: 31 AF XY: 0.588 AC XY: 43673 AN XY: 74272

African (AFR) AF: 0.643 AC: 26643 AN: 41440

American (AMR) AF: 0.540 AC: 8245 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2462 AN: 3468

East Asian (EAS) AF: 0.622 AC: 3211 AN: 5162

South Asian (SAS) AF: 0.682 AC: 3278 AN: 4808

European-Finnish (FIN) AF: 0.490 AC: 5170 AN: 10552

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38896 AN: 67958

Other (OTH) AF: 0.594 AC: 1252 AN: 2108

Alfa AF: 0.578 Hom.: 49222

Bravo AF: 0.597

Asia WGS AF: 0.669 AC: 2328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5764455; hg19: chr22-44398524;