rs17414857

Variant names:

• chr8-102058073-T-C
• rs17414857
• ENST00000521599.5:c.-209-28977A>G

Variant summary

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

The ENST00000521599.5(NCALD):​c.-209-28977A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,126 control chromosomes in the GnomAD database, including 1,330 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 0.12 (1330 hom., cov: 32)
• Consequence: NCALD ENST00000521599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCALD	NM_001040624.2	c.-296-28977A>G		intron_variant	Intron 1 of 7		NP_001035714.1
NCALD	NM_001040625.2	c.-209-28977A>G		intron_variant	Intron 1 of 6		NP_001035715.1
NCALD	NM_001040626.2	c.-209-37784A>G		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.-209-28977A>G		intron_variant	Intron 1 of 6	1		ENSP00000428105.1
NCALD	ENST00000311028.4	c.-209-37784A>G		intron_variant	Intron 1 of 6	5		ENSP00000310587.3
NCALD	ENST00000395923.5	c.-122-37784A>G		intron_variant	Intron 1 of 5	5		ENSP00000379256.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18332 AN: 152008 Hom.: 1329 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0827

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0863

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.121 AC: 18353 AN: 152126 Hom.: 1330 Cov.: 32 AF XY: 0.120 AC XY: 8950 AN XY: 74388

African (AFR) AF: 0.198 AC: 8203 AN: 41452

American (AMR) AF: 0.127 AC: 1935 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3470

East Asian (EAS) AF: 0.0827 AC: 427 AN: 5166

South Asian (SAS) AF: 0.160 AC: 771 AN: 4808

European-Finnish (FIN) AF: 0.0262 AC: 278 AN: 10612

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0863 AC: 5871 AN: 68000

Other (OTH) AF: 0.143 AC: 302 AN: 2116

Alfa AF: 0.103 Hom.: 1707

Bravo AF: 0.129

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.82
PhyloP100		-0.18
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: rs17414857; hg19: chr8-103070301;