3-108058409-C-A

Variant names:

• chr3-108058409-C-A
• rs1218151856
• NM_001777.4:c.712G>T

Variant summary

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

The NM_001777.4(CD47):​c.712G>T​(p.Val238Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V238I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CD47 NM_001777.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• 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.712G>T	p.Val238Phe	missense	Exon 6 of 11	NP_001768.1	Q08722-1
	CD47	NM_001382306.1		c.712G>T	p.Val238Phe	missense	Exon 6 of 10	NP_001369235.1
	CD47	NM_198793.3		c.712G>T	p.Val238Phe	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.712G>T	p.Val238Phe	missense	Exon 6 of 11	ENSP00000355361.5	Q08722-1
	CD47	ENST00000355354.13	TSL:1	c.712G>T	p.Val238Phe	missense	Exon 6 of 9	ENSP00000347512.7	Q08722-3
	CD47	ENST00000887593.1		c.712G>T	p.Val238Phe	missense	Exon 6 of 12	ENSP00000557652.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412326 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 697398

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32804

American (AMR) AF: 0.00 AC: 0 AN: 37020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25222

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38162

South Asian (SAS) AF: 0.00 AC: 0 AN: 80182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084562

Other (OTH) AF: 0.00 AC: 0 AN: 58546

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Benign	0.033	D
Sift4G	Uncertain	0.017	D
Polyphen		0.27	B
Vest4		0.32
MutPred		0.67		Loss of helix (P = 0.1706)
MVP		0.39
MPC		1.3
ClinPred		0.55	D
GERP RS		3.7
PromoterAI		-0.097	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.081
gMVP		0.54
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: -24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1218151856; hg19: chr3-107777256; COSMIC: COSV107440807; COSMIC: COSV107440807;