22-36805773-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001315532.2(PVALB):c.305-4855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,826 control chromosomes in the GnomAD database, including 9,058 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 0.32 (9058 hom., cov: 31)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

PVALB (HGNC:9704): (parvalbumin) The protein encoded by this gene is a high affinity calcium ion-binding protein that is structurally and functionally similar to calmodulin and troponin C. The encoded protein is thought to be involved in muscle relaxation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

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 (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVALB	NM_001315532.2	c.305-4855G>A		intron_variant		ENST00000417718.7
PVALB	NM_002854.3	c.305-4855G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVALB	ENST00000417718.7	c.305-4855G>A		intron_variant		1	NM_001315532.2	P1
PVALB	ENST00000216200.9	c.305-4855G>A		intron_variant		1		P1
PVALB	ENST00000404171.1	c.209-4855G>A		intron_variant		2
PVALB	ENST00000406910.6	c.*31-4855G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48360 AN: 151704 Hom.: 9059 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.318 AC: 48355 AN: 151826 Hom.: 9058 Cov.: 31 AF XY: 0.316 AC XY: 23437 AN XY: 74194

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.347

Alfa AF: 0.388 Hom.: 11816

Bravo AF: 0.302

Asia WGS AF: 0.189 AC: 657 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.7
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs2284021; hg19: chr22-37201817;