rs2022068

Variant names:

• chr22-36803762-A-G
• rs2022068
• NM_001315532.2:c.305-2844T>C

Variant summary

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

The NM_001315532.2(PVALB):​c.305-2844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 149,450 control chromosomes in the GnomAD database, including 30,461 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 0.62 (30461 hom., cov: 26)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.305-2844T>C		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.305-2844T>C		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.305-2844T>C		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.305-2844T>C		intron_variant	Intron 4 of 4	1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.*31-2844T>C		intron_variant	Intron 4 of 4	3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.209-2844T>C		intron_variant	Intron 3 of 3	2		ENSP00000386089.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 93014 AN: 149334 Hom.: 30440 Cov.: 26

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.623 AC: 93075 AN: 149450 Hom.: 30461 Cov.: 26 AF XY: 0.615 AC XY: 44794 AN XY: 72818

African (AFR) AF: 0.811 AC: 32720 AN: 40340

American (AMR) AF: 0.506 AC: 7535 AN: 14890

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1901 AN: 3450

East Asian (EAS) AF: 0.308 AC: 1554 AN: 5044

South Asian (SAS) AF: 0.454 AC: 2159 AN: 4756

European-Finnish (FIN) AF: 0.607 AC: 6083 AN: 10020

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.581 AC: 39298 AN: 67674

Other (OTH) AF: 0.576 AC: 1199 AN: 2082

Alfa AF: 0.594 Hom.: 70521

Bravo AF: 0.626

Asia WGS AF: 0.414 AC: 1432 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.49
PhyloP100		-1.2
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: rs2022068; hg19: chr22-37199806;