rs12171125

Variant names:

• chr22-36805406-A-G
• rs12171125
• NM_001315532.2:c.305-4488T>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.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 NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 4 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=-0.91).
• 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 rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.305-4488T>C		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.305-4488T>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.305-4488T>C		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.305-4488T>C		intron_variant	Intron 4 of 4	1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.*31-4488T>C		intron_variant	Intron 4 of 4	3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.209-4488T>C		intron_variant	Intron 3 of 3	2		ENSP00000386089.1

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

African (AFR) AF: 0.341 AC: 14146 AN: 41480

American (AMR) AF: 0.181 AC: 2764 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3470

East Asian (EAS) AF: 0.136 AC: 705 AN: 5186

South Asian (SAS) AF: 0.178 AC: 856 AN: 4820

European-Finnish (FIN) AF: 0.207 AC: 2194 AN: 10586

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10075 AN: 67986

Other (OTH) AF: 0.171 AC: 361 AN: 2116

Alfa AF: 0.199 Hom.: 490

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
PhyloP100		-0.16
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: rs12171125; hg19: chr22-37201450;