3-108080081-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001777.4(CD47):​c.310G>A​(p.Asp104Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,992 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CD47
NM_001777.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.219
Variant links:
Genes affected
CD47 (HGNC:1682): (CD47 molecule) This gene encodes a membrane protein, which is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix. The encoded protein is also a receptor for the C-terminal cell binding domain of thrombospondin, and it may play a role in membrane transport and signal transduction. This gene has broad tissue distribution, and is reduced in expression on Rh erythrocytes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD47NM_001777.4 linkc.310G>A p.Asp104Asn missense_variant Exon 2 of 11 ENST00000361309.6 NP_001768.1 Q08722-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD47ENST00000361309.6 linkc.310G>A p.Asp104Asn missense_variant Exon 2 of 11 1 NM_001777.4 ENSP00000355361.5 Q08722-1
CD47ENST00000355354.13 linkc.310G>A p.Asp104Asn missense_variant Exon 2 of 9 1 ENSP00000347512.7 Q08722-3
CD47ENST00000644850.1 linkc.175G>A p.Asp59Asn missense_variant Exon 2 of 5 ENSP00000493750.1 A0A2R8Y484

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
249060
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135132
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460992
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726772
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000828
AC:
1
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 05, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.310G>A (p.D104N) alteration is located in exon 2 (coding exon 2) of the CD47 gene. This alteration results from a G to A substitution at nucleotide position 310, causing the aspartic acid (D) at amino acid position 104 to be replaced by an asparagine (N). 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
Benign
0.11
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
.;T;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.68
T;T;T
M_CAP
Benign
0.0059
T
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;L;.
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-2.5
D;D;.
REVEL
Benign
0.16
Sift
Uncertain
0.0030
D;D;.
Sift4G
Uncertain
0.013
D;D;.
Polyphen
0.96
D;D;.
Vest4
0.093
MutPred
0.76
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;
MVP
0.32
MPC
0.41
ClinPred
0.56
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.28
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs760735393; hg19: chr3-107798928; API