3-108058351-C-T

Variant names:

• chr3-108058351-C-T
• rs1188363393
• NM_001777.4:c.770G>A

Variant summary

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

The NM_001777.4(CD47):​c.770G>A​(p.Ser257Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CD47 NM_001777.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52
• Publications: 1 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.770G>A	p.Ser257Asn	missense	Exon 6 of 11	NP_001768.1	Q08722-1
	CD47	NM_001382306.1		c.770G>A	p.Ser257Asn	missense	Exon 6 of 10	NP_001369235.1
	CD47	NM_198793.3		c.770G>A	p.Ser257Asn	missense	Exon 6 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.770G>A	p.Ser257Asn	missense	Exon 6 of 11	ENSP00000355361.5	Q08722-1
	CD47	ENST00000355354.13	TSL:1	c.770G>A	p.Ser257Asn	missense	Exon 6 of 9	ENSP00000347512.7	Q08722-3
	CD47	ENST00000887593.1		c.770G>A	p.Ser257Asn	missense	Exon 6 of 12	ENSP00000557652.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 173082 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407592 Hom.: 0 Cov.: 28 AF XY: 0.00000144 AC XY: 1 AN XY: 695034

African (AFR) AF: 0.00 AC: 0 AN: 32546

American (AMR) AF: 0.00 AC: 0 AN: 36314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25136

East Asian (EAS) AF: 0.00 AC: 0 AN: 37748

South Asian (SAS) AF: 0.00 AC: 0 AN: 79922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1081880

Other (OTH) AF: 0.00 AC: 0 AN: 58388

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0051	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Benign	0.065	T
Sift4G	Benign	0.30	T
Polyphen		0.95	P
Vest4		0.47
MutPred		0.69		Loss of glycosylation at S257 (P = 0.0118)
MVP		0.46
MPC		0.75
ClinPred		0.86	D
GERP RS		5.8
PromoterAI		0.043	Neutral
Varity_R		0.11
gMVP		0.32
Mutation Taster		=79/21	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

dbSNP: rs1188363393; hg19: chr3-107777198;