rs5750311

Positions:

• chr22-36812742-A-G
• chr22-36812742-A-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+904T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,276 control chromosomes in the GnomAD database, including 65,298 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 (65298 hom., cov: 33)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVALB	NM_001315532.2	c.304+904T>C		intron_variant		ENST00000417718.7
PVALB	NM_002854.3	c.304+904T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVALB	ENST00000417718.7	c.304+904T>C		intron_variant		1	NM_001315532.2	P1
PVALB	ENST00000216200.9	c.304+904T>C		intron_variant		1		P1
PVALB	ENST00000404171.1	c.208+904T>C		intron_variant		2
PVALB	ENST00000406910.6	c.300+904T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140862 AN: 152158 Hom.: 65266 Cov.: 33

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.926 AC: 140948 AN: 152276 Hom.: 65298 Cov.: 33 AF XY: 0.924 AC XY: 68778 AN XY: 74446

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.923

Alfa AF: 0.928 Hom.: 12808

Bravo AF: 0.921

Asia WGS AF: 0.896 AC: 3116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.58

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: rs5750311; hg19: chr22-37208786;