rs517868

chr8-101900802-A-Gchr8-101900802-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCALD	NM_001040624.2	c.-106-13575T>C		intron_variant
NCALD	NM_001040625.2	c.-20+15007T>C		intron_variant
NCALD	NM_001040626.2	c.-106-13575T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCALD	ENST00000521599.5	c.-20+15007T>C		intron_variant		1		P1
NCALD	ENST00000311028.4	c.-106-13575T>C		intron_variant		5		P1
NCALD	ENST00000395923.5	c.-20+15007T>C		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.300

Alfa AF: 0.263 Hom.: 696

Bravo AF: 0.353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	6.4
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs517868; hg19: chr8-102913030;