dbSNP rs13253373: NCALD:c.-123+64A>T (chr8-102124506-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001040630.2(NCALD):c.-123+64A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00075 ( 5 hom., cov: 5)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NCALD
NM_001040630.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.67

Publications

1 publications found

Variant links:

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]

NCALD links:

ENSG00000310378 (HGNC:):

ENSG00000310378 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-102124506-T-A is Benign according to our data. Variant chr8-102124506-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2658716.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
NCALD	NM_001040630.2	c.-123+64A>T	intron	N/A	NP_001035720.1	P61601
NCALD	NM_001040624.2	c.-566A>T	upstream_gene	N/A	NP_001035714.1	P61601
NCALD	NM_001040625.2	c.-479A>T	upstream_gene	N/A	NP_001035715.1	P61601

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCALD	ENST00000395923.5	TSL:5	c.-123+64A>T	intron	N/A	ENSP00000379256.1	P61601
NCALD	ENST00000522206.5	TSL:4	c.-241+121A>T	intron	N/A	ENSP00000429296.1	E5RIX3
NCALD	ENST00000522078.5	TSL:4	c.-210+64A>T	intron	N/A	ENSP00000429162.1	E5RJA1

Frequencies

GnomAD3 genomes

AF:

0.000755

AC:

AN:

62238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000638

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000330

Gnomad OTH

AF:

0.00134

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.000755

AC:

AN:

62272

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

29838

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

18380

American (AMR)

AF:

0.00

AC:

AN:

5832

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1436

East Asian (EAS)

AF:

0.000639

AC:

AN:

3128

South Asian (SAS)

AF:

0.0169

AC:

AN:

1832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000330

AC:

AN:

27248

Other (OTH)

AF:

0.00134

AC:

AN:

748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.602

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.37

PhyloP100

-2.7

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over