3-108080081-C-T

Variant names:

• chr3-108080081-C-T
• rs760735393
• NM_001777.4:c.310G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.219
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.310G>A	p.Asp104Asn	missense	Exon 2 of 11	NP_001768.1	Q08722-1
	CD47	NM_001382306.1		c.310G>A	p.Asp104Asn	missense	Exon 2 of 10	NP_001369235.1
	CD47	NM_198793.3		c.310G>A	p.Asp104Asn	missense	Exon 2 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.310G>A	p.Asp104Asn	missense	Exon 2 of 11	ENSP00000355361.5	Q08722-1
	CD47	ENST00000355354.13	TSL:1	c.310G>A	p.Asp104Asn	missense	Exon 2 of 9	ENSP00000347512.7	Q08722-3
	CD47	ENST00000887593.1		c.310G>A	p.Asp104Asn	missense	Exon 2 of 12	ENSP00000557652.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 249060 AF XY: 0.00

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111342

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	0.11
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
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.22
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.96	D
Vest4		0.093
MutPred		0.76		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
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs760735393; hg19: chr3-107798928;