22-36814612-T-C

Variant names:

• chr22-36814612-T-C
• rs2269511
• NM_001315532.2:c.194+491A>G

Variant summary

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

The NM_001315532.2(PVALB):​c.194+491A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,936 control chromosomes in the GnomAD database, including 36,882 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 0.69 (36882 hom., cov: 30)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001315532.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVALB	NM_001315532.2	MANE Select	c.194+491A>G		intron	N/A	NP_001302461.1	P20472
	PVALB	NM_002854.3		c.194+491A>G		intron	N/A	NP_002845.1	P20472

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVALB	ENST00000417718.7	TSL:1 MANE Select	c.194+491A>G		intron	N/A	ENSP00000400247.2	P20472
	PVALB	ENST00000216200.9	TSL:1	c.194+491A>G		intron	N/A	ENSP00000216200.5	P20472
	PVALB	ENST00000912200.1		c.194+491A>G		intron	N/A	ENSP00000582259.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104550 AN: 151818 Hom.: 36868 Cov.: 30

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.689 AC: 104609 AN: 151936 Hom.: 36882 Cov.: 30 AF XY: 0.686 AC XY: 50976 AN XY: 74276

African (AFR) AF: 0.536 AC: 22165 AN: 41386

American (AMR) AF: 0.676 AC: 10322 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2866 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3747 AN: 5156

South Asian (SAS) AF: 0.561 AC: 2694 AN: 4802

European-Finnish (FIN) AF: 0.743 AC: 7849 AN: 10570

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52515 AN: 67968

Other (OTH) AF: 0.730 AC: 1542 AN: 2112

Alfa AF: 0.741 Hom.: 138618

Bravo AF: 0.678

Asia WGS AF: 0.647 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.80
PhyloP100		0.21
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: rs2269511; hg19: chr22-37210656;