rs517811

Variant names:

• chr8-101932635-G-A
• rs517811
• ENST00000521599.5:c.-69-16777C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-101932635-G-A
• chr8-101932635-G-C
• chr8-101932635-G-T

Variant summary

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

The ENST00000521599.5(NCALD):​c.-69-16777C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,876 control chromosomes in the GnomAD database, including 27,899 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 0.60 (27899 hom., cov: 31)
• Consequence: NCALD ENST00000521599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCALD	NM_001040624.2	c.-156-16777C>T		intron_variant	Intron 3 of 7		NP_001035714.1
NCALD	NM_001040625.2	c.-69-16777C>T		intron_variant	Intron 3 of 6		NP_001035715.1
NCALD	NM_001040626.2	c.-156-16777C>T		intron_variant	Intron 2 of 6		NP_001035716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCALD	ENST00000521599.5	c.-69-16777C>T		intron_variant	Intron 3 of 6	1		ENSP00000428105.1
NCALD	ENST00000311028.4	c.-156-16777C>T		intron_variant	Intron 2 of 6	5		ENSP00000310587.3
NCALD	ENST00000395923.5	c.-69-16777C>T		intron_variant	Intron 2 of 5	5		ENSP00000379256.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91811 AN: 151758 Hom.: 27878 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.605 AC: 91877 AN: 151876 Hom.: 27899 Cov.: 31 AF XY: 0.602 AC XY: 44686 AN XY: 74236

African (AFR) AF: 0.602 AC: 24925 AN: 41392

American (AMR) AF: 0.615 AC: 9388 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2410 AN: 5160

South Asian (SAS) AF: 0.645 AC: 3108 AN: 4818

European-Finnish (FIN) AF: 0.565 AC: 5942 AN: 10514

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41792 AN: 67936

Other (OTH) AF: 0.602 AC: 1270 AN: 2110

Alfa AF: 0.608 Hom.: 115320

Bravo AF: 0.604

Asia WGS AF: 0.586 AC: 2036 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.028
DANN	Benign	0.46
PhyloP100		-2.7
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: rs517811; hg19: chr8-102944863;