22-36805773-C-T

Variant names:

• chr22-36805773-C-T
• rs2284021
• NM_001315532.2:c.305-4855G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.305-4855G>A		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.305-4855G>A		intron_variant	Intron 4 of 4		NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.305-4855G>A		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.305-4855G>A		intron_variant	Intron 4 of 4	1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.*31-4855G>A		intron_variant	Intron 4 of 4	3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.209-4855G>A		intron_variant	Intron 3 of 3	2		ENSP00000386089.1

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

African (AFR) AF: 0.128 AC: 5319 AN: 41406

American (AMR) AF: 0.295 AC: 4490 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3466

East Asian (EAS) AF: 0.176 AC: 904 AN: 5134

South Asian (SAS) AF: 0.284 AC: 1367 AN: 4808

European-Finnish (FIN) AF: 0.401 AC: 4224 AN: 10542

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.431 AC: 29275 AN: 67922

Other (OTH) AF: 0.347 AC: 732 AN: 2110

Alfa AF: 0.386 Hom.: 14093

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
PhyloP100		-0.016
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2284021; hg19: chr22-37201817;