22-36812742-A-G

Variant names:

• chr22-36812742-A-G
• rs5750311
• NM_001315532.2:c.304+904T>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.304+904T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,276 control chromosomes in the GnomAD database, including 65,298 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 (65298 hom., cov: 33)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 1 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 = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVALB	NM_001315532.2	c.304+904T>C		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+904T>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.304+904T>C		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.304+904T>C		intron_variant	Intron 4 of 4	1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.298+904T>C		intron_variant	Intron 3 of 4	3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.208+904T>C		intron_variant	Intron 3 of 3	2		ENSP00000386089.1

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140862 AN: 152158 Hom.: 65266 Cov.: 33

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.926 AC: 140948 AN: 152276 Hom.: 65298 Cov.: 33 AF XY: 0.924 AC XY: 68778 AN XY: 74446

African (AFR) AF: 0.957 AC: 39738 AN: 41544

American (AMR) AF: 0.865 AC: 13234 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3148 AN: 3472

East Asian (EAS) AF: 0.890 AC: 4601 AN: 5170

South Asian (SAS) AF: 0.844 AC: 4067 AN: 4818

European-Finnish (FIN) AF: 0.953 AC: 10113 AN: 10612

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62953 AN: 68030

Other (OTH) AF: 0.923 AC: 1954 AN: 2116

Alfa AF: 0.928 Hom.: 22198

Bravo AF: 0.921

Asia WGS AF: 0.896 AC: 3116 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	3.0
DANN	Benign	0.58
PhyloP100		-0.057
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: rs5750311; hg19: chr22-37208786;