rs501344

Positions:

• chr8-102102345-G-A
• chr8-102102345-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521599.5(NCALD):​c.-210+21892C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,892 control chromosomes in the GnomAD database, including 7,715 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 0.31 (7715 hom., cov: 32)
• Consequence: NCALD ENST00000521599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCALD	NM_001040624.2	c.-297+21892C>T		intron_variant			NP_001035714.1
NCALD	NM_001040625.2	c.-210+21892C>T		intron_variant			NP_001035715.1
NCALD	NM_001040626.2	c.-210+21892C>T		intron_variant			NP_001035716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCALD	ENST00000521599.5	c.-210+21892C>T		intron_variant		1		ENSP00000428105	P1
NCALD	ENST00000311028.4	c.-210+21892C>T		intron_variant		5		ENSP00000310587	P1
NCALD	ENST00000395923.5	c.-123+22225C>T		intron_variant		5		ENSP00000379256	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46830 AN: 151776 Hom.: 7717 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.308 AC: 46856 AN: 151892 Hom.: 7715 Cov.: 32 AF XY: 0.309 AC XY: 22916 AN XY: 74226

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.324

Alfa AF: 0.348 Hom.: 12421

Bravo AF: 0.303

Asia WGS AF: 0.384 AC: 1336 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	2.5
DANN	Benign	0.57

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: rs501344; hg19: chr8-103114573;