8-101769493-G-A

Variant names:

• chr8-101769493-G-A
• rs6988793
• NM_032041.3:c.-20+21369C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032041.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCALD	NM_032041.3	MANE Select	c.-20+21369C>T		intron	N/A	NP_114430.2
	NCALD	NM_001040624.2		c.-19-49845C>T		intron	N/A	NP_001035714.1
	NCALD	NM_001040625.2		c.-19-49845C>T		intron	N/A	NP_001035715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCALD	ENST00000220931.11	TSL:1 MANE Select	c.-20+21369C>T		intron	N/A	ENSP00000220931.6
	NCALD	ENST00000521599.5	TSL:1	c.-19-49845C>T		intron	N/A	ENSP00000428105.1
	NCALD	ENST00000522951.5	TSL:5	c.-20+21369C>T		intron	N/A	ENSP00000428781.1

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

African (AFR) AF: 0.405 AC: 16743 AN: 41380

American (AMR) AF: 0.620 AC: 9468 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2584 AN: 3472

East Asian (EAS) AF: 0.702 AC: 3636 AN: 5176

South Asian (SAS) AF: 0.682 AC: 3288 AN: 4822

European-Finnish (FIN) AF: 0.838 AC: 8868 AN: 10588

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51530 AN: 67980

Other (OTH) AF: 0.670 AC: 1412 AN: 2108

Alfa AF: 0.715 Hom.: 20881

Bravo AF: 0.619

Asia WGS AF: 0.626 AC: 2175 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.96
PhyloP100		-0.97
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: rs6988793; hg19: chr8-102781721;