NM_001315532.2:c.304+394C>G

Variant names:

• chr22-36813252-G-C
• rs4820255
• NM_001315532.2:c.304+394C>G

Variant summary

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

The NM_001315532.2(PVALB):​c.304+394C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,172 control chromosomes in the GnomAD database, including 64,909 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 0.92 (64909 hom., cov: 29)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+394C>G		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+394C>G		intron_variant	Intron 4 of 4		NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.304+394C>G		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140399 AN: 152054 Hom.: 64884 Cov.: 29

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.921

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

GnomAD4 genome AF: 0.923 AC: 140475 AN: 152172 Hom.: 64909 Cov.: 29 AF XY: 0.921 AC XY: 68528 AN XY: 74390

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.920

Alfa AF: 0.923 Hom.: 30920

Bravo AF: 0.917

Asia WGS AF: 0.891 AC: 3099 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.57

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: rs4820255; hg19: chr22-37209296;