22-36813403-C-T

Variant names:

• chr22-36813403-C-T
• rs4821536
• NM_001315532.2:c.304+243G>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+243G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 475,430 control chromosomes in the GnomAD database, including 188,658 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 (56905 hom., cov: 30)
  • Exomes 𝑓: 0.90 (131753 hom.)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+243G>A		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+243G>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+243G>A		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130880 AN: 152008 Hom.: 56886 Cov.: 30

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.901 AC: 291347 AN: 323304 Hom.: 131753 Cov.: 3 AF XY: 0.900 AC XY: 150527 AN XY: 167194

African (AFR) AF: 0.730 AC: 7438 AN: 10194

American (AMR) AF: 0.821 AC: 11741 AN: 14300

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 9399 AN: 10400

East Asian (EAS) AF: 0.864 AC: 21941 AN: 25384

South Asian (SAS) AF: 0.835 AC: 17750 AN: 21252

European-Finnish (FIN) AF: 0.949 AC: 20747 AN: 21858

Middle Eastern (MID) AF: 0.890 AC: 1599 AN: 1796

European-Non Finnish (NFE) AF: 0.923 AC: 183027 AN: 198308

Other (OTH) AF: 0.894 AC: 17705 AN: 19812

GnomAD4 genome AF: 0.861 AC: 130942 AN: 152126 Hom.: 56905 Cov.: 30 AF XY: 0.862 AC XY: 64106 AN XY: 74368

African (AFR) AF: 0.730 AC: 30273 AN: 41442

American (AMR) AF: 0.841 AC: 12866 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3147 AN: 3472

East Asian (EAS) AF: 0.889 AC: 4593 AN: 5164

South Asian (SAS) AF: 0.843 AC: 4065 AN: 4822

European-Finnish (FIN) AF: 0.953 AC: 10101 AN: 10600

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62893 AN: 68016

Other (OTH) AF: 0.884 AC: 1866 AN: 2112

Alfa AF: 0.897 Hom.: 31090

Bravo AF: 0.845

Asia WGS AF: 0.880 AC: 3059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.16
PhyloP100		-1.9
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: rs4821536; hg19: chr22-37209447;