22-36803762-A-G

Position:

• chr22-36803762-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	UniProt
PVALB	NM_001315532.2	c.305-2844T>C		intron_variant		ENST00000417718.7
PVALB	NM_002854.3	c.305-2844T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVALB	ENST00000417718.7	c.305-2844T>C		intron_variant		1	NM_001315532.2	P1
PVALB	ENST00000216200.9	c.305-2844T>C		intron_variant		1		P1
PVALB	ENST00000404171.1	c.209-2844T>C		intron_variant		2
PVALB	ENST00000406910.6	c.*31-2844T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.576

Alfa AF: 0.578 Hom.: 24486

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

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: rs2022068; hg19: chr22-37199806;