ENST00000521599.5:c.-209-43713C>A

Variant names:

• chr8-102072809-G-T
• rs11784583
• ENST00000521599.5:c.-209-43713C>A

Variant summary

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

The ENST00000521599.5(NCALD):​c.-209-43713C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,032 control chromosomes in the GnomAD database, including 2,572 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 0.17 (2572 hom., cov: 32)
• Consequence: NCALD ENST00000521599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• Publications: 2 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]

LOC124901997 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 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.-296-43713C>A		intron	N/A	NP_001035714.1
	NCALD	NM_001040625.2		c.-209-43713C>A		intron	N/A	NP_001035715.1
	NCALD	NM_001040626.2		c.-210+51428C>A		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.-209-43713C>A		intron	N/A	ENSP00000428105.1
	NCALD	ENST00000311028.4	TSL:5	c.-210+51428C>A		intron	N/A	ENSP00000310587.3
	NCALD	ENST00000395923.5	TSL:5	c.-123+51761C>A		intron	N/A	ENSP00000379256.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25876 AN: 151914 Hom.: 2564 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0400

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.170 AC: 25914 AN: 152032 Hom.: 2572 Cov.: 32 AF XY: 0.169 AC XY: 12534 AN XY: 74310

African (AFR) AF: 0.272 AC: 11261 AN: 41456

American (AMR) AF: 0.127 AC: 1947 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3468

East Asian (EAS) AF: 0.0401 AC: 208 AN: 5182

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1736 AN: 10540

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9541 AN: 67966

Other (OTH) AF: 0.164 AC: 346 AN: 2116

Alfa AF: 0.0870 Hom.: 134

Bravo AF: 0.174

Asia WGS AF: 0.0780 AC: 270 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.48
PhyloP100		-0.83
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: rs11784583; hg19: chr8-103085037;