22-36808185-G-T

Position:

• chr22-36808185-G-T

Variant summary

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

The NM_001315532.2(PVALB):​c.304+5461C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 152,330 control chromosomes in the GnomAD database, including 66,353 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 0.93 (66353 hom., cov: 33)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+5461C>A		intron_variant		ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+5461C>A		intron_variant			NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.304+5461C>A		intron_variant		1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.304+5461C>A		intron_variant		1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.*30+3290C>A		intron_variant		3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.208+5461C>A		intron_variant		2		ENSP00000386089.1

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141946 AN: 152212 Hom.: 66306 Cov.: 33

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.929

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

GnomAD4 genome AF: 0.932 AC: 142047 AN: 152330 Hom.: 66353 Cov.: 33 AF XY: 0.930 AC XY: 69293 AN XY: 74486

Gnomad4 AFR AF: 0.982

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.952

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.928

Alfa AF: 0.931 Hom.: 13440

Bravo AF: 0.928

Asia WGS AF: 0.888 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.79

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: rs2284024; hg19: chr22-37204229;