rs6988793

Positions:

• chr8-101769493-G-A
• chr8-101769493-G-T

Variant summary

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

The NM_032041.3(NCALD):​c.-20+21369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,998 control chromosomes in the GnomAD database, including 33,820 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 0.65 (33820 hom., cov: 32)
• Consequence: NCALD NM_032041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCALD	NM_032041.3	c.-20+21369C>T		intron_variant		ENST00000220931.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCALD	ENST00000220931.11	c.-20+21369C>T		intron_variant		1	NM_032041.3	P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98481 AN: 151880 Hom.: 33822 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.648 AC: 98498 AN: 151998 Hom.: 33820 Cov.: 32 AF XY: 0.653 AC XY: 48556 AN XY: 74318

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.670

Alfa AF: 0.715 Hom.: 18668

Bravo AF: 0.619

Asia WGS AF: 0.626 AC: 2175 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.96

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: rs6988793; hg19: chr8-102781721;