8-102124496-GCCC-GCCCC

Variant names:

• chr8-102124496-G-GC
• rs1046926270
• NM_001040630.2:c.-123+73dupG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001040630.2(NCALD):​c.-123+73dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 75,628 control chromosomes in the GnomAD database, including 42 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0037 (42 hom., cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCALD NM_001040630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920

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.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00366 (277/75628) while in subpopulation EAS AF= 0.027 (72/2668). AF 95% confidence interval is 0.022. There are 42 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCALD	NM_001040630.2	c.-123+73dupG		intron_variant	Intron 1 of 5		NP_001035720.1
NCALD	XM_047422315.1	c.-210+73dupG		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+73_-123+74insG		intron_variant	Intron 1 of 5	5		ENSP00000379256.1
NCALD	ENST00000522206.5	c.-241+130_-241+131insG		intron_variant	Intron 1 of 4	4		ENSP00000429296.1
NCALD	ENST00000522078.5	c.-210+73_-210+74insG		intron_variant	Intron 1 of 4	4		ENSP00000429162.1

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 279 AN: 75578 Hom.: 42 Cov.: 25

Gnomad AFR AF: 0.00330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00369

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.00768

Gnomad FIN AF: 0.00110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00274

Gnomad OTH AF: 0.00321

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 188 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00366 AC: 277 AN: 75628 Hom.: 42 Cov.: 25 AF XY: 0.00389 AC XY: 142 AN XY: 36490

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.00369

Gnomad4 EAS AF: 0.0270

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.00110

Gnomad4 NFE AF: 0.00274

Gnomad4 OTH AF: 0.00320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1046926270; hg19: chr8-103136724;