22-36814612-T-C

Position:

• chr22-36814612-T-C

Variant summary

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

The ENST00000417718.7(PVALB):​c.194+491A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,936 control chromosomes in the GnomAD database, including 36,882 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 0.69 (36882 hom., cov: 30)
• Consequence: PVALB ENST00000417718.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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]

PVALB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.194+491A>G		intron_variant		ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.194+491A>G		intron_variant			NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.194+491A>G		intron_variant		1	NM_001315532.2	ENSP00000400247.2

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104550 AN: 151818 Hom.: 36868 Cov.: 30

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.689 AC: 104609 AN: 151936 Hom.: 36882 Cov.: 30 AF XY: 0.686 AC XY: 50976 AN XY: 74276

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.730

Alfa AF: 0.755 Hom.: 57494

Bravo AF: 0.678

Asia WGS AF: 0.647 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.80

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: rs2269511; hg19: chr22-37210656;