rs6987078

Variant names:

• chr8-102032733-G-A
• rs6987078
• ENST00000521599.5:c.-209-3637C>T

Variant summary

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

The ENST00000521599.5(NCALD):​c.-209-3637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,624 control chromosomes in the GnomAD database, including 5,752 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 0.26 (5752 hom., cov: 30)
• Consequence: NCALD ENST00000521599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCALD	NM_001040624.2	c.-296-3637C>T		intron_variant	Intron 1 of 7		NP_001035714.1
NCALD	NM_001040625.2	c.-209-3637C>T		intron_variant	Intron 1 of 6		NP_001035715.1
NCALD	NM_001040626.2	c.-209-12444C>T		intron_variant	Intron 1 of 6		NP_001035716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCALD	ENST00000521599.5	c.-209-3637C>T		intron_variant	Intron 1 of 6	1		ENSP00000428105.1
NCALD	ENST00000311028.4	c.-209-12444C>T		intron_variant	Intron 1 of 6	5		ENSP00000310587.3
NCALD	ENST00000395923.5	c.-122-12444C>T		intron_variant	Intron 1 of 5	5		ENSP00000379256.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40031 AN: 151508 Hom.: 5746 Cov.: 30

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.264 AC: 40075 AN: 151624 Hom.: 5752 Cov.: 30 AF XY: 0.265 AC XY: 19586 AN XY: 74048

African (AFR) AF: 0.356 AC: 14706 AN: 41286

American (AMR) AF: 0.215 AC: 3275 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1634 AN: 5148

South Asian (SAS) AF: 0.447 AC: 2137 AN: 4784

European-Finnish (FIN) AF: 0.185 AC: 1931 AN: 10460

Middle Eastern (MID) AF: 0.255 AC: 74 AN: 290

European-Non Finnish (NFE) AF: 0.218 AC: 14837 AN: 67940

Other (OTH) AF: 0.270 AC: 569 AN: 2108

Alfa AF: 0.236 Hom.: 7598

Bravo AF: 0.265

Asia WGS AF: 0.419 AC: 1456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.7
DANN	Benign	0.85
PhyloP100		0.047
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

Other links and lift over

dbSNP: rs6987078; hg19: chr8-103044961;