3-108060760-T-G

Variant names:

• chr3-108060760-T-G
• NM_001777.4:c.583A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001777.4(CD47):​c.583A>C​(p.Ile195Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: CD47 NM_001777.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.877
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24882498).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001777.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD47	NM_001777.4	MANE Select	c.583A>C	p.Ile195Leu	missense	Exon 4 of 11	NP_001768.1	Q08722-1
	CD47	NM_001382306.1		c.583A>C	p.Ile195Leu	missense	Exon 4 of 10	NP_001369235.1
	CD47	NM_198793.3		c.583A>C	p.Ile195Leu	missense	Exon 4 of 9	NP_942088.1	Q08722-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD47	ENST00000361309.6	TSL:1 MANE Select	c.583A>C	p.Ile195Leu	missense	Exon 4 of 11	ENSP00000355361.5	Q08722-1
	CD47	ENST00000355354.13	TSL:1	c.583A>C	p.Ile195Leu	missense	Exon 4 of 9	ENSP00000347512.7	Q08722-3
	CD47	ENST00000887593.1		c.583A>C	p.Ile195Leu	missense	Exon 4 of 12	ENSP00000557652.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.88
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.057
Sift	Benign	0.10	T
Sift4G	Benign	0.18	T
Polyphen		0.023	B
Vest4		0.44
MutPred		0.50		Loss of sheet (P = 0.1158)
MVP		0.28
MPC		1.2
ClinPred		0.89	D
GERP RS		3.8
Varity_R		0.091
gMVP		0.54
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr3-107779607;