Genetic Variant CD47:p.Asp104Asn (chr3-108080081-C-T) – ACMG Classification: Uncertain_significance (2 pts)

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

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]

CD47 links:

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
CD47	NM_001777.4 link	c.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	UniProt
CD47	ENST00000361309.6 link	c.310G>A	p.Asp104Asn	missense_variant	Exon 2 of 11	1	NM_001777.4	ENSP00000355361.5	Q08722-1
CD47	ENST00000355354.13 link	c.310G>A	p.Asp104Asn	missense_variant	Exon 2 of 9	1		ENSP00000347512.7	Q08722-3
CD47	ENST00000644850.1 link	c.175G>A	p.Asp59Asn	missense_variant	Exon 2 of 5			ENSP00000493750.1	A0A2R8Y484

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249060

Hom.:

AF XY:

0.00

AC XY:

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:

AN:

1460992

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

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.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

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

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

.;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.0059

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;.

PrimateAI

Benign

0.33

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over