chr22-36808185-G-T

Variant names:

• chr22-36808185-G-T
• rs2284024
• NM_001315532.2:c.304+5461C>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+5461C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 152,330 control chromosomes in the GnomAD database, including 66,353 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 0.93 (66353 hom., cov: 33)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+5461C>A		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+5461C>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+5461C>A		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.304+5461C>A		intron_variant	Intron 4 of 4	1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.*30+3290C>A		intron_variant	Intron 4 of 4	3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.208+5461C>A		intron_variant	Intron 3 of 3	2		ENSP00000386089.1

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141946 AN: 152212 Hom.: 66306 Cov.: 33

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.929

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

GnomAD4 genome AF: 0.932 AC: 142047 AN: 152330 Hom.: 66353 Cov.: 33 AF XY: 0.930 AC XY: 69293 AN XY: 74486

African (AFR) AF: 0.982 AC: 40819 AN: 41574

American (AMR) AF: 0.867 AC: 13273 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3149 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4589 AN: 5178

South Asian (SAS) AF: 0.838 AC: 4046 AN: 4830

European-Finnish (FIN) AF: 0.952 AC: 10123 AN: 10628

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62949 AN: 68030

Other (OTH) AF: 0.928 AC: 1958 AN: 2110

Alfa AF: 0.925 Hom.: 24058

Bravo AF: 0.928

Asia WGS AF: 0.888 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.79
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: rs2284024; hg19: chr22-37204229;