3-108058409-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001777.4(CD47):​c.712G>A​(p.Val238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,564,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

CD47
NM_001777.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07911256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD47NM_001777.4 linkc.712G>A p.Val238Ile missense_variant Exon 6 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.712G>A p.Val238Ile missense_variant Exon 6 of 11 1 NM_001777.4 ENSP00000355361.5 Q08722-1
CD47ENST00000355354.13 linkc.712G>A p.Val238Ile missense_variant Exon 6 of 9 1 ENSP00000347512.7 Q08722-3
CD47ENST00000517766.5 linkc.100G>A p.Val34Ile missense_variant Exon 2 of 6 2 ENSP00000430843.1 H0YC40
CD47ENST00000398258.7 linkc.-50G>A upstream_gene_variant 3 ENSP00000381309.3 H7BYS8

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000393
AC:
7
AN:
178156
Hom.:
0
AF XY:
0.0000427
AC XY:
4
AN XY:
93766
show subpopulations
Gnomad AFR exome
AF:
0.0000949
Gnomad AMR exome
AF:
0.0000387
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000419
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000406
Gnomad OTH exome
AF:
0.000213
GnomAD4 exome
AF:
0.0000241
AC:
34
AN:
1412326
Hom.:
0
Cov.:
29
AF XY:
0.0000229
AC XY:
16
AN XY:
697398
show subpopulations
Gnomad4 AFR exome
AF:
0.000122
Gnomad4 AMR exome
AF:
0.0000540
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000240
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000332
Hom.:
0
Bravo
AF:
0.0000416

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.712G>A (p.V238I) alteration is located in exon 6 (coding exon 6) of the CD47 gene. This alteration results from a G to A substitution at nucleotide position 712, causing the valine (V) at amino acid position 238 to be replaced by an isoleucine (I). 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
0.13
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
.;T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.16
N
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.079
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;L
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.79
N;N
REVEL
Benign
0.077
Sift
Benign
0.042
D;D
Sift4G
Benign
0.14
T;T
Polyphen
0.15
B;B
Vest4
0.11
MVP
0.23
MPC
0.47
ClinPred
0.033
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.030
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs1218151856; hg19: chr3-107777256; COSMIC: COSV100790136; COSMIC: COSV100790136; API