rs12171125

Positions:

• chr22-36805406-A-G

Variant summary

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

The ENST00000417718.7(PVALB):​c.305-4488T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,136 control chromosomes in the GnomAD database, including 3,885 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 0.21 (3885 hom., cov: 32)
• Consequence: PVALB ENST00000417718.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

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 = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.305-4488T>C		intron_variant		ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.305-4488T>C		intron_variant			NP_002845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVALB	ENST00000417718.7	c.305-4488T>C		intron_variant		1	NM_001315532.2	ENSP00000400247	P1
PVALB	ENST00000216200.9	c.305-4488T>C		intron_variant		1		ENSP00000216200	P1
PVALB	ENST00000404171.1	c.209-4488T>C		intron_variant		2		ENSP00000386089
PVALB	ENST00000406910.6	c.*31-4488T>C		intron_variant		3		ENSP00000384735

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31586 AN: 152018 Hom.: 3884 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.208 AC: 31607 AN: 152136 Hom.: 3885 Cov.: 32 AF XY: 0.207 AC XY: 15421 AN XY: 74388

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.171

Alfa AF: 0.195 Hom.: 444

Bravo AF: 0.212

Asia WGS AF: 0.213 AC: 742 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	2.9
DANN	Benign	0.44

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: rs12171125; hg19: chr22-37201450;