rs892954

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181351.5(NCAM1):​c.53-87131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,074 control chromosomes in the GnomAD database, including 48,329 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 0.80 ( 48329 hom., cov: 31)

Consequence

NCAM1
NM_181351.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.914
Variant links:
Genes affected
NCAM1 (HGNC:7656): (neural cell adhesion molecule 1) This gene encodes a cell adhesion protein which is a member of the immunoglobulin superfamily. The encoded protein is involved in cell-to-cell interactions as well as cell-matrix interactions during development and differentiation. The encoded protein plays a role in the development of the nervous system by regulating neurogenesis, neurite outgrowth, and cell migration. This protein is also involved in the expansion of T lymphocytes, B lymphocytes and natural killer (NK) cells which play an important role in immune surveillance. This protein plays a role in signal transduction by interacting with fibroblast growth factor receptors, N-cadherin and other components of the extracellular matrix and by triggering signalling cascades involving FYN-focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K). One prominent isoform of this gene, cell surface molecule CD56, plays a role in several myeloproliferative disorders such as acute myeloid leukemia and differential expression of this gene is associated with differential disease progression. For example, increased expression of CD56 is correlated with lower survival in acute myeloid leukemia patients whereas increased severity of COVID-19 is correlated with decreased abundance of CD56-expressing NK cells in peripheral blood. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NCAM1NM_181351.5 linkuse as main transcriptc.53-87131A>G intron_variant ENST00000316851.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NCAM1ENST00000316851.12 linkuse as main transcriptc.53-87131A>G intron_variant 5 NM_181351.5 P3P13591-2

Frequencies

GnomAD3 genomes
AF:
0.796
AC:
120886
AN:
151956
Hom.:
48282
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.875
Gnomad AMI
AF:
0.799
Gnomad AMR
AF:
0.779
Gnomad ASJ
AF:
0.747
Gnomad EAS
AF:
0.737
Gnomad SAS
AF:
0.692
Gnomad FIN
AF:
0.804
Gnomad MID
AF:
0.677
Gnomad NFE
AF:
0.765
Gnomad OTH
AF:
0.788
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.796
AC:
120988
AN:
152074
Hom.:
48329
Cov.:
31
AF XY:
0.795
AC XY:
59120
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.875
Gnomad4 AMR
AF:
0.779
Gnomad4 ASJ
AF:
0.747
Gnomad4 EAS
AF:
0.737
Gnomad4 SAS
AF:
0.691
Gnomad4 FIN
AF:
0.804
Gnomad4 NFE
AF:
0.764
Gnomad4 OTH
AF:
0.787
Alfa
AF:
0.788
Hom.:
8017
Bravo
AF:
0.798
Asia WGS
AF:
0.720
AC:
2504
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.18
DANN
Benign
0.40

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: rs892954; hg19: chr11-112985970; API