22-36806662-C-T

Variant names:

• chr22-36806662-C-T
• rs736721
• NM_001315532.2:c.305-5744G>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.305-5744G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,988 control chromosomes in the GnomAD database, including 3,252 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 0.19 (3252 hom., cov: 31)
• Consequence: PVALB NM_001315532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001315532.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVALB	NM_001315532.2	MANE Select	c.305-5744G>A		intron	N/A	NP_001302461.1
	PVALB	NM_002854.3		c.305-5744G>A		intron	N/A	NP_002845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVALB	ENST00000417718.7	TSL:1 MANE Select	c.305-5744G>A		intron	N/A	ENSP00000400247.2
	PVALB	ENST00000216200.9	TSL:1	c.305-5744G>A		intron	N/A	ENSP00000216200.5
	PVALB	ENST00000406910.6	TSL:3	c.*30+4813G>A		intron	N/A	ENSP00000384735.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29475 AN: 151870 Hom.: 3251 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.194 AC: 29485 AN: 151988 Hom.: 3252 Cov.: 31 AF XY: 0.194 AC XY: 14389 AN XY: 74298

African (AFR) AF: 0.296 AC: 12261 AN: 41400

American (AMR) AF: 0.175 AC: 2665 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 295 AN: 3470

East Asian (EAS) AF: 0.135 AC: 697 AN: 5178

South Asian (SAS) AF: 0.164 AC: 792 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2194 AN: 10580

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10048 AN: 67978

Other (OTH) AF: 0.160 AC: 338 AN: 2106

Alfa AF: 0.0996 Hom.: 143

Bravo AF: 0.197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.92
PhyloP100		-0.13
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: rs736721; hg19: chr22-37202706;