chr22-44004818-G-A

Variant names:

• chr22-44004818-G-A
• rs6006611
• ENST00000406477.7:c.211+5145G>A

Variant summary

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

The ENST00000406477.7(PARVB):​c.211+5145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,964 control chromosomes in the GnomAD database, including 15,082 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 0.44 (15082 hom., cov: 32)
• Consequence: PARVB ENST00000406477.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_001003828.3	c.211+5145G>A		intron_variant	Intron 2 of 13		NP_001003828.1
PARVB	XM_024452236.2	c.211+5145G>A		intron_variant	Intron 2 of 12		XP_024308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000406477.7	c.211+5145G>A		intron_variant	Intron 2 of 13	1		ENSP00000384515.3
SAMM50	ENST00000465768.1	n.80-4659G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67017 AN: 151844 Hom.: 15063 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.441 AC: 67070 AN: 151964 Hom.: 15082 Cov.: 32 AF XY: 0.434 AC XY: 32231 AN XY: 74248

African (AFR) AF: 0.411 AC: 17051 AN: 41444

American (AMR) AF: 0.455 AC: 6952 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1940 AN: 3466

East Asian (EAS) AF: 0.496 AC: 2559 AN: 5160

South Asian (SAS) AF: 0.439 AC: 2112 AN: 4812

European-Finnish (FIN) AF: 0.333 AC: 3509 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31559 AN: 67948

Other (OTH) AF: 0.473 AC: 997 AN: 2110

Alfa AF: 0.463 Hom.: 42753

Bravo AF: 0.452

Asia WGS AF: 0.489 AC: 1702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.62
PhyloP100		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6006611; hg19: chr22-44400698;