8-101744623-A-G

Variant names:

• chr8-101744623-A-G
• rs6468792
• NM_032041.3:c.-19-24975T>C

Variant summary

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

The NM_032041.3(NCALD):​c.-19-24975T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,066 control chromosomes in the GnomAD database, including 31,339 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 0.62 (31339 hom., cov: 32)
• Consequence: NCALD NM_032041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCALD	NM_032041.3	c.-19-24975T>C		intron_variant	Intron 1 of 3	ENST00000220931.11	NP_114430.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCALD	ENST00000220931.11	c.-19-24975T>C		intron_variant	Intron 1 of 3	1	NM_032041.3	ENSP00000220931.6

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93569 AN: 151948 Hom.: 31341 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.615 AC: 93574 AN: 152066 Hom.: 31339 Cov.: 32 AF XY: 0.620 AC XY: 46107 AN XY: 74352

African (AFR) AF: 0.339 AC: 14068 AN: 41444

American (AMR) AF: 0.565 AC: 8618 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3470

East Asian (EAS) AF: 0.657 AC: 3385 AN: 5156

South Asian (SAS) AF: 0.659 AC: 3173 AN: 4816

European-Finnish (FIN) AF: 0.816 AC: 8650 AN: 10604

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50795 AN: 68000

Other (OTH) AF: 0.650 AC: 1373 AN: 2112

Alfa AF: 0.702 Hom.: 161035

Bravo AF: 0.581

Asia WGS AF: 0.593 AC: 2061 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		0.23
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: rs6468792; hg19: chr8-102756851;