ENST00000521599.5:c.-20+15007T>C

Variant names:

• chr8-101900802-A-G
• rs517868
• ENST00000521599.5:c.-20+15007T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521599.5(NCALD):​c.-20+15007T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,740 control chromosomes in the GnomAD database, including 9,908 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 0.33 (9908 hom., cov: 32)
• Consequence: NCALD ENST00000521599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 1 publications found

Genes affected

NCALD (HGNC:7655): (neurocalcin delta) This gene encodes a member of the neuronal calcium sensor (NCS) family of calcium-binding proteins. The protein contains an N-terminal myristoylation signal and four EF-hand calcium binding loops. The protein is cytosolic at resting calcium levels; however, elevated intracellular calcium levels induce a conformational change that exposes the myristoyl group, resulting in protein association with membranes and partial co-localization with the perinuclear trans-golgi network. The protein is thought to be a regulator of G protein-coupled receptor signal transduction. Several alternatively spliced variants of this gene have been determined, all of which encode the same protein; additional variants may exist but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521599.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCALD	NM_001040624.2		c.-106-13575T>C		intron	N/A	NP_001035714.1	P61601
	NCALD	NM_001040625.2		c.-20+15007T>C		intron	N/A	NP_001035715.1	P61601
	NCALD	NM_001040626.2		c.-106-13575T>C		intron	N/A	NP_001035716.1	B2RB70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCALD	ENST00000521599.5	TSL:1	c.-20+15007T>C		intron	N/A	ENSP00000428105.1	P61601
	NCALD	ENST00000311028.4	TSL:5	c.-106-13575T>C		intron	N/A	ENSP00000310587.3	P61601
	NCALD	ENST00000395923.5	TSL:5	c.-20+15007T>C		intron	N/A	ENSP00000379256.1	P61601

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49991 AN: 151622 Hom.: 9886 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.330 AC: 50061 AN: 151740 Hom.: 9908 Cov.: 32 AF XY: 0.329 AC XY: 24410 AN XY: 74162

African (AFR) AF: 0.544 AC: 22495 AN: 41388

American (AMR) AF: 0.352 AC: 5359 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 858 AN: 3468

East Asian (EAS) AF: 0.392 AC: 2021 AN: 5156

South Asian (SAS) AF: 0.317 AC: 1525 AN: 4814

European-Finnish (FIN) AF: 0.185 AC: 1954 AN: 10544

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.221 AC: 15021 AN: 67836

Other (OTH) AF: 0.300 AC: 628 AN: 2096

Alfa AF: 0.263 Hom.: 696

Bravo AF: 0.353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.4
DANN	Benign	0.83
PhyloP100		-0.41
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs517868;

hg19: chr8-102913030;