rs6006611

Positions:

• chr22-44004818-G-A
• chr22-44004818-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	Protein	UniProt
PARVB	NM_001003828.3	c.211+5145G>A		intron_variant			NP_001003828.1
PARVB	XM_024452236.2	c.211+5145G>A		intron_variant			XP_024308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000406477.7	c.211+5145G>A		intron_variant		1		ENSP00000384515
SAMM50	ENST00000465768.1	n.80-4659G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.473

Alfa AF: 0.464 Hom.: 25492

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6006611; hg19: chr22-44400698;