22-36813403-C-T

Position:

• chr22-36813403-C-T

Variant summary

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

The ENST00000417718.7(PVALB):​c.304+243G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 475,430 control chromosomes in the GnomAD database, including 188,658 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 0.86 (56905 hom., cov: 30)
  • Exomes 𝑓: 0.90 (131753 hom.)
• Consequence: PVALB ENST00000417718.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+243G>A		intron_variant		ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+243G>A		intron_variant			NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.304+243G>A		intron_variant		1	NM_001315532.2	ENSP00000400247	P1

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130880 AN: 152008 Hom.: 56886 Cov.: 30

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.901 AC: 291347 AN: 323304 Hom.: 131753 Cov.: 3 AF XY: 0.900 AC XY: 150527 AN XY: 167194

Gnomad4 AFR exome AF: 0.730

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.904

Gnomad4 EAS exome AF: 0.864

Gnomad4 SAS exome AF: 0.835

Gnomad4 FIN exome AF: 0.949

Gnomad4 NFE exome AF: 0.923

Gnomad4 OTH exome AF: 0.894

GnomAD4 genome AF: 0.861 AC: 130942 AN: 152126 Hom.: 56905 Cov.: 30 AF XY: 0.862 AC XY: 64106 AN XY: 74368

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.884

Alfa AF: 0.897 Hom.: 27613

Bravo AF: 0.845

Asia WGS AF: 0.880 AC: 3059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4821536; hg19: chr22-37209447;