chr22-29727700-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2

The NM_182527.3(CABP7):ā€‹c.148A>Gā€‹(p.Asn50Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

CABP7
NM_182527.3 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19
Variant links:
Genes affected
CABP7 (HGNC:20834): (calcium binding protein 7) Predicted to enable calcium ion binding activity. Located in trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity CABP7_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.3829166).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CABP7NM_182527.3 linkuse as main transcriptc.148A>G p.Asn50Asp missense_variant 2/5 ENST00000216144.4 NP_872333.1 Q86V35

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CABP7ENST00000216144.4 linkuse as main transcriptc.148A>G p.Asn50Asp missense_variant 2/51 NM_182527.3 ENSP00000216144.3 Q86V35

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461460
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727050
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ 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:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 20, 2022The c.148A>G (p.N50D) alteration is located in exon 2 (coding exon 2) of the CABP7 gene. This alteration results from a A to G substitution at nucleotide position 148, causing the asparagine (N) at amino acid position 50 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
27
DANN
Uncertain
0.98
DEOGEN2
Benign
0.11
T
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
-0.98
N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.69
N
REVEL
Benign
0.26
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
1.0
D
Vest4
0.21
MutPred
0.58
Gain of disorder (P = 0.1009);
MVP
0.23
MPC
0.51
ClinPred
0.63
D
GERP RS
5.6
Varity_R
0.28
gMVP
0.85

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1342999594; hg19: chr22-30123689; API