rs12545537

Variant names:

• chr8-101755024-T-C
• rs12545537
• NM_032041.3:c.-19-35376A>G

Variant summary

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

The NM_032041.3(NCALD):​c.-19-35376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,084 control chromosomes in the GnomAD database, including 35,716 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 0.67 (35716 hom., cov: 32)
• Consequence: NCALD NM_032041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCALD	NM_032041.3	c.-19-35376A>G		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.-19-35376A>G		intron_variant	Intron 1 of 3	1	NM_032041.3	ENSP00000220931.6

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102471 AN: 151966 Hom.: 35710 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.674 AC: 102506 AN: 152084 Hom.: 35716 Cov.: 32 AF XY: 0.680 AC XY: 50583 AN XY: 74354

African (AFR) AF: 0.488 AC: 20218 AN: 41460

American (AMR) AF: 0.633 AC: 9667 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2587 AN: 3472

East Asian (EAS) AF: 0.772 AC: 3989 AN: 5170

South Asian (SAS) AF: 0.754 AC: 3636 AN: 4820

European-Finnish (FIN) AF: 0.832 AC: 8824 AN: 10600

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51135 AN: 67970

Other (OTH) AF: 0.707 AC: 1492 AN: 2110

Alfa AF: 0.722 Hom.: 125216

Bravo AF: 0.648

Asia WGS AF: 0.684 AC: 2379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.21
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: rs12545537; hg19: chr8-102767252;