22-44002644-A-G

Position:

• chr22-44002644-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_001003828.3	c.211+2971A>G		intron_variant
PARVB	XM_024452236.2	c.211+2971A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000406477.7	c.211+2971A>G		intron_variant		1
SAMM50	ENST00000465768.1	n.80-6833A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.594

Alfa AF: 0.576 Hom.: 32518

Bravo AF: 0.597

Asia WGS AF: 0.669 AC: 2328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5764455; hg19: chr22-44398524;