chr8-102040149-G-A

Variant names:

• chr8-102040149-G-A
• rs16868941
• ENST00000521599.5:c.-209-11053C>T

Variant summary

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

The ENST00000521599.5(NCALD):​c.-209-11053C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,116 control chromosomes in the GnomAD database, including 2,500 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 0.18 (2500 hom., cov: 32)
• Consequence: NCALD ENST00000521599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCALD	NM_001040624.2		c.-296-11053C>T		intron	N/A	NP_001035714.1
	NCALD	NM_001040625.2		c.-209-11053C>T		intron	N/A	NP_001035715.1
	NCALD	NM_001040626.2		c.-209-19860C>T		intron	N/A	NP_001035716.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCALD	ENST00000521599.5	TSL:1	c.-209-11053C>T		intron	N/A	ENSP00000428105.1
	NCALD	ENST00000311028.4	TSL:5	c.-209-19860C>T		intron	N/A	ENSP00000310587.3
	NCALD	ENST00000395923.5	TSL:5	c.-122-19860C>T		intron	N/A	ENSP00000379256.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26798 AN: 151998 Hom.: 2498 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.176 AC: 26822 AN: 152116 Hom.: 2500 Cov.: 32 AF XY: 0.174 AC XY: 12923 AN XY: 74384

African (AFR) AF: 0.185 AC: 7676 AN: 41486

American (AMR) AF: 0.117 AC: 1796 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3466

East Asian (EAS) AF: 0.0636 AC: 330 AN: 5188

South Asian (SAS) AF: 0.177 AC: 850 AN: 4808

European-Finnish (FIN) AF: 0.187 AC: 1984 AN: 10590

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13175 AN: 67972

Other (OTH) AF: 0.159 AC: 336 AN: 2114

Alfa AF: 0.187 Hom.: 9598

Bravo AF: 0.171

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.36
PhyloP100		-0.17
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: rs16868941; hg19: chr8-103052377;