22-36812105-G-T

Variant names:

• chr22-36812105-G-T
• rs739031
• NM_001315532.2:c.304+1541C>A

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+1541C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,240 control chromosomes in the GnomAD database, including 57,070 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 0.86 (57070 hom., cov: 32)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+1541C>A		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+1541C>A		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+1541C>A		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.304+1541C>A		intron_variant	Intron 4 of 4	1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.299-581C>A		intron_variant	Intron 3 of 4	3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.208+1541C>A		intron_variant	Intron 3 of 3	2		ENSP00000386089.1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131170 AN: 152122 Hom.: 57044 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.885

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

GnomAD4 genome AF: 0.862 AC: 131242 AN: 152240 Hom.: 57070 Cov.: 32 AF XY: 0.863 AC XY: 64248 AN XY: 74458

African (AFR) AF: 0.737 AC: 30601 AN: 41502

American (AMR) AF: 0.841 AC: 12861 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3140 AN: 3472

East Asian (EAS) AF: 0.887 AC: 4596 AN: 5184

South Asian (SAS) AF: 0.836 AC: 4030 AN: 4820

European-Finnish (FIN) AF: 0.953 AC: 10113 AN: 10614

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62897 AN: 68032

Other (OTH) AF: 0.884 AC: 1868 AN: 2112

Alfa AF: 0.897 Hom.: 134014

Bravo AF: 0.847

Asia WGS AF: 0.879 AC: 3056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-0.018
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs739031; hg19: chr22-37208149;