rs4821535

Positions:

• chr22-36812908-A-C
• chr22-36812908-A-G
• chr22-36812908-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001315532.2(PVALB):​c.304+738T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+738T>G		intron_variant		ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+738T>G		intron_variant			NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.304+738T>G		intron_variant		1	NM_001315532.2	ENSP00000400247	P1
PVALB	ENST00000216200.9	c.304+738T>G		intron_variant		1		ENSP00000216200	P1
PVALB	ENST00000404171.1	c.208+738T>G		intron_variant		2		ENSP00000386089
PVALB	ENST00000406910.6	c.300+738T>G		intron_variant		3		ENSP00000384735

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4821535; hg19: chr22-37208952;