8-102035959-A-G

Variant names:

• chr8-102035959-A-G
• rs11780799
• ENST00000521599.5:c.-209-6863T>C

Variant summary

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

The ENST00000521599.5(NCALD):​c.-209-6863T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,690 control chromosomes in the GnomAD database, including 21,440 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 0.52 (21440 hom., cov: 29)
• Consequence: NCALD ENST00000521599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• 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]

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 (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCALD	NM_001040624.2	c.-296-6863T>C		intron_variant	Intron 1 of 7		NP_001035714.1
NCALD	NM_001040625.2	c.-209-6863T>C		intron_variant	Intron 1 of 6		NP_001035715.1
NCALD	NM_001040626.2	c.-209-15670T>C		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.-209-6863T>C		intron_variant	Intron 1 of 6	1		ENSP00000428105.1
NCALD	ENST00000311028.4	c.-209-15670T>C		intron_variant	Intron 1 of 6	5		ENSP00000310587.3
NCALD	ENST00000395923.5	c.-122-15670T>C		intron_variant	Intron 1 of 5	5		ENSP00000379256.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78576 AN: 151572 Hom.: 21402 Cov.: 29

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.519 AC: 78662 AN: 151690 Hom.: 21440 Cov.: 29 AF XY: 0.509 AC XY: 37692 AN XY: 74118

African (AFR) AF: 0.637 AC: 26315 AN: 41300

American (AMR) AF: 0.374 AC: 5706 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1687 AN: 3466

East Asian (EAS) AF: 0.112 AC: 581 AN: 5180

South Asian (SAS) AF: 0.341 AC: 1635 AN: 4796

European-Finnish (FIN) AF: 0.489 AC: 5127 AN: 10480

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35887 AN: 67906

Other (OTH) AF: 0.485 AC: 1025 AN: 2114

Alfa AF: 0.549 Hom.: 9472

Bravo AF: 0.517

Asia WGS AF: 0.283 AC: 987 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	4.1
DANN	Benign	0.70
PhyloP100		0.053
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: rs11780799; hg19: chr8-103048187;