22-36815245-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001315532.2(PVALB):c.62-10C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,614,086 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (24 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (45 hom.)
• Consequence: PVALB NM_001315532.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.008743
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-36815245-G-T is Benign according to our data. Variant chr22-36815245-G-T is described in ClinVar as [Benign]. Clinvar id is 781617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1625/152308) while in subpopulation AFR AF= 0.0366 (1523/41558). AF 95% confidence interval is 0.0351. There are 24 homozygotes in gnomad4. There are 766 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVALB	NM_001315532.2	c.62-10C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000417718.7
PVALB	NM_002854.3	c.62-10C>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVALB	ENST00000417718.7	c.62-10C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001315532.2	P1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1627 AN: 152190 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00338 AC: 849 AN: 251382 Hom.: 12 AF XY: 0.00291 AC XY: 396 AN XY: 135874

Gnomad AFR exome AF: 0.0356

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00683

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00149 AC: 2173 AN: 1461778 Hom.: 45 Cov.: 31 AF XY: 0.00151 AC XY: 1098 AN XY: 727192

Gnomad4 AFR exome AF: 0.0389

Gnomad4 AMR exome AF: 0.00192

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00708

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00237

GnomAD4 genome AF: 0.0107 AC: 1625 AN: 152308 Hom.: 24 Cov.: 32 AF XY: 0.0103 AC XY: 766 AN XY: 74474

Gnomad4 AFR AF: 0.0366

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00734 Hom.: 6

Bravo AF: 0.0121

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	8.8
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0087
dbscSNV1_RF	Benign	0.092
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: rs145809194; hg19: chr22-37211289;