8-102124506-T-C

Variant names:

• chr8-102124506-T-C
• rs13253373
• NM_001040630.2:c.-123+64A>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_001040630.2(NCALD):​c.-123+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.42 (4755 hom., cov: 5)
  • Exomes 𝑓: 0.088 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCALD NM_001040630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0882 (3/34) while in subpopulation NFE AF= 0.136 (3/22). AF 95% confidence interval is 0.0372. There are 0 homozygotes in gnomad4_exome. There are 1 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCALD	NM_001040630.2	c.-123+64A>G		intron_variant	Intron 1 of 5		NP_001035720.1
NCALD	XM_047422315.1	c.-210+64A>G		intron_variant	Intron 1 of 6		XP_047278271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCALD	ENST00000395923.5	c.-123+64A>G		intron_variant	Intron 1 of 5	5		ENSP00000379256.1
NCALD	ENST00000522206.5	c.-241+121A>G		intron_variant	Intron 1 of 4	4		ENSP00000429296.1
NCALD	ENST00000522078.5	c.-210+64A>G		intron_variant	Intron 1 of 4	4		ENSP00000429162.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 23949 AN: 56354 Hom.: 4752 Cov.: 5 FAILED QC

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.0882 AC: 3 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.425 AC: 23959 AN: 56384 Hom.: 4755 Cov.: 5 AF XY: 0.406 AC XY: 10989 AN XY: 27058

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.0
DANN	Benign	0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13253373; hg19: chr8-103136734;