22-36810297-T-G

Variant names:

• chr22-36810297-T-G
• rs4820254
• NM_001315532.2:c.304+3349A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001315532.2(PVALB):​c.304+3349A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,108 control chromosomes in the GnomAD database, including 21,104 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 0.50 (21104 hom., cov: 32)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+3349A>C		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+3349A>C		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+3349A>C		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.304+3349A>C		intron_variant	Intron 4 of 4	1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.*30+1178A>C		intron_variant	Intron 4 of 4	3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.208+3349A>C		intron_variant	Intron 3 of 3	2		ENSP00000386089.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76640 AN: 151990 Hom.: 21083 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.504 AC: 76702 AN: 152108 Hom.: 21104 Cov.: 32 AF XY: 0.498 AC XY: 37039 AN XY: 74348

African (AFR) AF: 0.733 AC: 30404 AN: 41502

American (AMR) AF: 0.406 AC: 6204 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3470

East Asian (EAS) AF: 0.193 AC: 999 AN: 5170

South Asian (SAS) AF: 0.352 AC: 1695 AN: 4822

European-Finnish (FIN) AF: 0.466 AC: 4923 AN: 10574

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29654 AN: 67972

Other (OTH) AF: 0.460 AC: 970 AN: 2110

Alfa AF: 0.452 Hom.: 66290

Bravo AF: 0.509

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.66
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4820254; hg19: chr22-37206341;