chr22-36812908-A-G

Variant names:

• chr22-36812908-A-G
• rs4821535
• NM_001315532.2:c.304+738T>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+738T>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 152,292 control chromosomes in the GnomAD database, including 65,313 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 (65313 hom., cov: 32)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• 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+738T>C		intron_variant	Intron 3 of 3	ENST00000417718.7	NP_001302461.1
PVALB	NM_002854.3	c.304+738T>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+738T>C		intron_variant	Intron 3 of 3	1	NM_001315532.2	ENSP00000400247.2
PVALB	ENST00000216200.9	c.304+738T>C		intron_variant	Intron 4 of 4	1		ENSP00000216200.5
PVALB	ENST00000406910.6	c.298+738T>C		intron_variant	Intron 3 of 4	3		ENSP00000384735.2
PVALB	ENST00000404171.1	c.208+738T>C		intron_variant	Intron 3 of 3	2		ENSP00000386089.1

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140892 AN: 152174 Hom.: 65281 Cov.: 32

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.926

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

GnomAD4 genome AF: 0.926 AC: 140978 AN: 152292 Hom.: 65313 Cov.: 32 AF XY: 0.924 AC XY: 68798 AN XY: 74460

African (AFR) AF: 0.956 AC: 39750 AN: 41558

American (AMR) AF: 0.865 AC: 13230 AN: 15298

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

East Asian (EAS) AF: 0.891 AC: 4616 AN: 5182

South Asian (SAS) AF: 0.844 AC: 4073 AN: 4824

European-Finnish (FIN) AF: 0.953 AC: 10107 AN: 10608

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

European-Non Finnish (NFE) AF: 0.925 AC: 62962 AN: 68034

Other (OTH) AF: 0.925 AC: 1952 AN: 2110

Alfa AF: 0.925 Hom.: 23080

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	3.2
DANN	Benign	0.52
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4821535; hg19: chr22-37208952;