rs1131863

Positions:

• chr8-101688067-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032041.3(NCALD):​c.*1242A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,212 control chromosomes in the GnomAD database, including 4,292 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 0.23 (4283 hom., cov: 32)
  • Exomes 𝑓: 0.28 (9 hom.)
• Consequence: NCALD NM_032041.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCALD	NM_032041.3	c.*1242A>G		3_prime_UTR_variant	4/4	ENST00000220931.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCALD	ENST00000220931.11	c.*1242A>G		3_prime_UTR_variant	4/4	1	NM_032041.3	P1
	ENST00000518749.1	n.237-902T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34329 AN: 151974 Hom.: 4292 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.283 AC: 34 AN: 120 Hom.: 9 Cov.: 0 AF XY: 0.278 AC XY: 15 AN XY: 54

Gnomad4 AMR exome AF: 0.286

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.226 AC: 34308 AN: 152092 Hom.: 4283 Cov.: 32 AF XY: 0.227 AC XY: 16907 AN XY: 74334

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.233

Alfa AF: 0.256 Hom.: 4620

Bravo AF: 0.226

Asia WGS AF: 0.267 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1131863; hg19: chr8-102700295;